J. Balzarini

In vitro synergistic activity against CCR5-tropic HIV-1 with combinations of potential candidate microbicide molecules HHA, KRV2110 and enfuvirtide (T20) (2009)

Jenabian, M. A., Saïdi, H., Charpentier, C., Van Herrewege, Y., Son, J. C., Schols, D., ...

OBJECTIVES: To block the different mechanisms of HIV mucosal transmission, it is likely that use of several microbicide molecules will lead to the best protection against HIV transmission. Indeed,...

Microwave-Assisted Synthesis of Imidazolylthiazolidin-4-ones as Potential Anti-HIV Agents (2009)

Modha, Sachinkumar; U0059367 JFA; CORA, Mehta, V.P., Ermolat'ev, D, Balzarini, J, Van Hecke, Kristof; U0012356 ;, Van Meervelt, Luc; U0014577 ;, ...

Synthesis and antiretroviral evaluation of new alkoxy and aryloxy phosphate derivatives of 3'-azido-3'-deoxythymidine (2008)

Tsotinis, A., Calogeropoulou, Theodora, Koufaki, Maria, Souli, C., Balzarini, J., DeClercq, E., ...

Journal URL: http://pubs.acs.org/journals/jmcmar/index.html

Ether phospholipid-AZT conjugates possessing anti-HIV and antitumor cell activity. Synthesis, conformational analysis, and study of their thermal effects on membrane bilayers (2008)

Mavromoustakos, Thomas, Calogeropoulou, Theodora, Koufaki, Maria, Kolocouris, A., Daliani, I., Demetzos, C., ...

Journal URL: http://pubs.acs.org/journals/jmcmar/index.html

Synthesis and Anti-Hiv Evaluation of Alkyl and Alkoxyethyl Phosphodiester Azt Derivatives (2008)

Calogeropoulou, Theodora, Koufaki, Maria, Tsotinis, A., Balzarini, J., Declercq, E., Makriyannis, A.

Journal URL: http://www.intmedpress.com/General/showSectionSub.cfm?SectionID=2&SectionSubID=2&SectionSubSubID=10

Carbohydrate-binding agents (CBAs) inhibit HIV-1 infection in human primary monocyte-derived macrophages (MDMs) and efficiently prevent MDM-directed viral capture and subsequent transmission to CD4(+) T lymphocytes (2008)

POLLIELTA, M, SCHOLS, D, AQUARO, S, PEUMANS, WJ, Van Damme, Els, PERNO, CF, ...

From M-tuberculosis thymidine monophosphate kinase (TMPKmt) inhibitors towards mitochondrial thymidine kinase (TK-2) inhibitors (2008)

Van Calenbergh, Serge, Van Daele, I, Van Poecke, Sara, Froeyen, M, Munier Lehmann, H, Balzarini, J

Here, we report on the enzyme structure-aided design of a series of substituted 3'- or 5'-thiourea derivatives of beta- and alpha-thymidine, respectively, as thymidine monophosphate kinase inhibitors...

Thymidine analogs as potential antiviral agents (2008)

Yadav, Dipti, Rai, Diwakar, Balzarini, J., De Clercq, E., Singh, Ramendra K.

A dideoxythymidine analog, viz. 3′-N, N-dimethyl-2′-3′-dideoxythymidine (3) and its 5′-O-carboxyl ester prodrug derivatives (4–6) have been synthesized as probable antiviral agents. All...

Design and development of curcumin bioconjugates as antiviral agents (2008)

Rai, Diwakar, Yadav, Dipti, Balzarini, J., De Clercq, E., Singh, Ramendra K.

A number of curcumin bioconjugates with fatty acid, dipeptide and folic acid, viz. di-O-decanoyl curcumin (2), di-O-tryptophanylphenylalanine curcumin (3), di-O-bis-(γ, γ)folyl curcumin (4),...

Nucleoside Diphosphate Prodrugs (2008)

Meier, C., Jessen, H. J., Balzarini, J.

Nucleoside analogs are widely applied in antiviral and antitumor therapy. A severe limitation of these compounds arises from the need of biotransformation to the eventually active nucleoside...

The carbohydrate-binding plant lectins and the non-peptidic antibiotic pradimicin A target the glycans of the coronavirus envelope glycoproteins (2007)

Van Der Meer, F. J. U. M., De Haan, C. A. M., Schuurman, N. M. P., Haijema, B. J., Verheije, M. H., Bosch, B. J., ...

Objectives Many enveloped viruses carry carbohydrate-containing proteins on their surface. These glycoproteins are key to the infection process as they are mediators of the receptor binding and...

The carbohydrate-binding plant lectins and the non-peptidic antibiotic pradimicin A target the glycans of the coronavirus envelope glycoproteins (2007)

Meer, F.J.U.M. Van Der, Haan, C.A.M. De, Schuurman, N.M., Haijema, B.J., Verheije, M.H., Bosch, B.J., ...

Objectives: Many enveloped viruses carry carbohydrate-containing proteins on their surface. These glycoproteins are key to the infection process as they are mediators of the receptor binding and...

Rational design of 5'-thiourea-substituted alpha-thymidine analogues as thymidine monophosphate kinase inhibitors capable of inhibiting mycobacterial growth (2007)

Van Daele, Ineke, MUNIER-LEHMANN, H, FROEYEN, M, BALZARINI, J, Van Calenbergh, Serge

Carbohydrate-binding agents (CBAs) potently inhibit HIV infection in human primary monocytes/macrophages and efficiently prevent viral capture and subsequent transmission to CD+4 T lymphocytes (2007)

POLLICITA, M, AQUARO, S, PEUMANS, WJ, Van Damme, Els, PERNO, CF, SCHOLS, D, ...

Antiviral activity of carbohydrate-binding agents against Nidovirales in cell culture (2007)

VAN DER MEER, FJUM, DE HAAN, CAM, SCHUMMAN, NMP, HAIJEMA, BJ, PEUMANS, WJ, Van Damme, Els, ...

Entry of hepatitis C virus and human immunodeficiency virus is selectively inhibited by carbohydrate-binding agents but not by polyanions (2007)

BERTAUX, C, DAELEMANS, D, MEERTENS, L, CORMIER, EG, REINUS, JF, PEUMANS, WJ, ...

Plant lectins are potent inhibitors of coronaviruses by interfering with two targets in the viral replication cycle (2007)

KEYAERTS, E, VIJGEN, L, PANNECOUQUE, C, Van Damme, Els, PEUMANS, W, EGBERINK, H, ...

A novel mannose-binding tuber lectin from Typhonium divaricatum (L.) Decne (family Araceae) with antiviral activity against HSV-II and anti-proliferative effect on human cancer cell lines (2007)

LUO, YT, XU, XC, LIU, JW, LI, J, SUN, YS, LIU, Z, ...

A novel tetrameric lectin from Lycoris aurea with four mannose binding sites per monomer (2007)

LIU, JW, XU, XC, LIU, JZ, BALZARINI, J, LUO, YT, KONG, Y, ...

Carbohydrate-binding agents (CBAs) selectively target the glycoproteins of the HCV and HIV envelope to prevent viral entry (2007)

BALZARINI, J, BERTAUX, C, DAELEMANS, D, MEERTENS, M, CORNIER, EG, REINUS, JF, ...

Carbohydrate-binding agents efficiently prevent dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN)-directed HIV-1 transmission to T lymphocytes (2007)

Balzarini, J., Van Herrewege, Y., Vermeire, K., Vanham, G., Schols, D.

Exposure of HIV-1 to dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN)-expressing B-lymphoblast Raji cells (Raji/DC-SIGN) but not to wild-type Raji/0 cells...

Enhanced toxicity of purine nucleoside analogs in cells expressing Drosophila melanogaster nucleoside kinase mutants (2006)

N Solaroli, M Johansson, J Balzarini, A Karlsson

Pyridine N-oxide derivatives are inhibitory to the human SARS and feline infectious peritonitis coronavirus in cell culture (2006)

Balzarini, J., Keyaerts, E., Vijgen, L., Meer, F. Van Der, Stevens, M., Clercq, E. De, ...

Anti-HIV I/II activity and molecular cloning of a novel mannose/sialic acid-binding lectin from rhizome of Polygonatum cyrtonema Hua (2006)

AN, J, LIU, JZ, WU, CF, LI, J, DAI, L, Van Damme, Els, ...

Mutational pathways, resistance profile, and side effects of cyanovirin relative to human immunodeficiency virus type 1 strains with N-glycan deletions in their gp120 envelopes (2006)

BALZARINI, J, VAN LAETHEM, K, PEUMANS, WJ, Van Damme, Els, BOLMSTEDT, A, GAGO, F, ...

Carbohydrate-binding agents cause deletions of highly conserved glycosylation sites in HIV GP120 - A new therapeutic concept to hit the Achilles heel of HIV (2005)

BALZARINI, J, VAN LAETHEM, K, HATSE, S, FROEYEN, M, PEUMANS, W, Van Damme, Els, ...

Marked depletion of glycosylation sites in HIV-1 gp120 under selection pressure by the mannose-specific plant lectins of Hippeastrum hybrid and Galanthus nivalis (2005)

BALZARINI, J, VAN LAETHEM, K, HATSE, S, FROEYEN, M, Van Damme, Els, BOLMSTEDT, A, ...

Mannose-specific plant lectins from the Amaryllidaceae family qualify as efficient microbicides for prevention of human immunodeficiency virus infection (2004)

BALZARINI, J, HATSE, S, VERMEIRE, K, PRINCEN, K, AQUARO, S, PERNO, CF, ...

Profile of resistance of human immunodeficiency virus to mannose-specific plant lectins (2004)

BALZARINI, J, VAN LAETHEM, K, HATSE, S, VERMEIRE, K, DE CLERCQ, ER, PEUMANS, W, ...

In vitro evaluation of nonnucleoside reverse transcriptase inhibitors UC-781 and TMC120-R147681 as human immunodeficiency virus microbicides (2004)

Van Herrewege, Y., Michiels, J., Van Roey, J., Fransen, K., Kestens, L., Balzarini, J., ...

An in vitro model of monocyte-derived dendritic cells (MO-DC) and CD4(+) T cells, representing the primary targets of sexual human immunodeficiency virus (HIV) transmission, was used to evaluate the...

Novel nucleotide analogues as potential substrates for TMPK, a key enzyme in the metabolism of AZT (2003)

Müller,H. C., Meier,C., Balzarini,J., Reinstein,Jochen

Novel cyclic and acyclic analogues of dTMP and AZTMP were synthesized from the corresponding cycloSal-phosphotriesters. This method yielded the nucleotides in good yields with a simple work-up....

[(18)F]FDG PET monitoring of tumour response to chemotherapy: does [(18)F]FDG uptake correlate with the viable tumour cell fraction? (2003)

Spaepen, Karoline; U0034608 JFA; CORA, Stroobants, Sigrid; U0014886 ;, Dupont, Patrick; U0016657 ;, Bormans, Guy; U0009552 ;, Balzarini, J, Verhoef, Gregor; U0003176 ;, ...

Because metabolic changes induced by chemotherapy precede the morphological changes, fluorine-18 fluorodeoxyglucose positron emission tomography ([(18)F]FDG PET) is thought to predict response to...

Metabolic and pharmacological characteristics of the bicyclic nucleoside analogues (BCNAs) as highly selective inhibitors of Varicella-Zoster virus (VZV) (2003)

Sienaert, R., Naesens, L., Brancale, A., Carangio, A., Andrei, G., Snoeck, R., ...

Novel nucleotide analogues as potential substrates for TMPK, a key enzyme in the metabolism of AZT (2003)

Müller, H. C., Meier, C., Balzarini, J., Reinstein, Jochen

Novel cyclic and acyclic analogues of dTMP and AZTMP were synthesized from the corresponding cycloSal-phosphotriesters. This method yielded the nucleotides in good yields with a simple work-up....

Database searching for thymidine and thymidylate kinase inhibitors using 3-dimensional structure based methods (2002)

Manallack, D, Pitt, W, Herdewijn, P, Balzarini, J, De Clecq, E, Sanderson, MR, ...

Lack of susceptibility of bicyclic nucleoside analogs, highly potent inhibitors of varicella-zoster virus, to the catabolic action of thymidine phosphorylase and dihydropyrimidine dehydrogenase (2002)

Balzarini, J., Sienaert, R., Liekens, S., Kuilenburg, A.B.P. Van, Carangio, A., Esnouf, R., ...

Metabolic activation of nucleoside and nucleotide reverse transcriptase inhibitors in dendritic and Langerhans cells (2002)

Balzarini, J., Van Herrewege, Y., Vanham, G.

Not the final published version

Activity of reverse transcriptase inhibitors in monocyte-derived dendritic cells: a possible in vitro model for postexposure prophylaxis of sexual HIV transmission (2002)

Van Herrewege, Y., Penne, L., Vereecken, C., Fransen, K., Van Der Groen, G., Kestens, L., ...

Because prevention of heterosexual HIV transmission is not always possible, it is important to develop effective strategies of postexposure prophylaxis (PEP). Since in vivo comparison of drug potency...

Early restaging positron emission tomography with 18F-fluorodeoxyglucose predicts outcome in patients with aggressive non-Hodgkin's lymphoma (2002)

Spaepen, K., Stroobants, S., Dupont, P., Vandenberghe, P., Thomas, J., De Groot, T., ...

Background: Less than half of all patients with aggressive non-Hodgkin’s lymphoma (NHL) are cured with standard chemotherapy. Therefore, it is important to distinguish between responders to...

Early restaging positron emmision tomography (PET) with 18F-fluorodeoxyglucose ((18)FDG) predicts outcome in patients with aggressive non Hodgkin's lymphoma (NHL) (2001)

Spaepen, Karoline; U0034608, Stroobants, S, Dupont, Patrick; U0016657 ;, Vanderberghe, P, Thomas, José; U0035480 ;, De Groot, T, ...

Solid dispersions of the antiviral agent UC-781 with Vitamin E-TPGS (2001)

Damian, F. ; JFA; CORA, Blaton, Norbert; U0008061 ;, Augustijns, Patrick; U0004215 ;, Naesens, L., Balzarini, J., Kinget, Renaat; U0016947 ;, ...

Physical stability of solid dispersions of the antiviral thiocarboxanilide UC-781 with PEG 6000, Gelucire 44/14 and PVP K30 (2001)

Damian, F. ; JFA; CORA, Blaton, Norbert; U0008061 ;, Augustijns, Patrick; U0004215 ;, Naesens, L., Balzarini, J., Kinget, Renaat; U0016947 ;, ...

Synthesis, Characterization and Antiviral Properties of Pd(II) Complexes With Penciclovir (2001)

A. Garoufis, K. Karidi, N. Hadjiliadis, S. Kasselouri, J. Kobe, J. Balzarini, ...

With the aim to improve and extend the antiviral activity of the antiherpic drug penciclovir, to a wider spectrum of viruses, we have synthesized and characterized new binary and ternary complexes of...

Multidrug-resistance protein 5 is a multispecific organic anion transporter able to transport nucleotide analogs (2000)

Wijnholds, J., Mol, C.A.A.M., Deemter, L. Van, Haas, M. De, Scheffer, G.J., Baas, F., ...

Oral absorption characteristics of the antiviral agent UC-781 (2000)

Augustijns, Patrick; U0004215 JFA; CORA, Van Gelder, J., Van Den Mooter, Guy; U0006817 ;, De Buck, S., Naesens, L., Balzarini, J., ...

An investigation of the thermal properties of binary solid dispersions of UC-781 with PEG6000 and Gelucire 44/14 by differential scanning calorimetry (2000)

Damian, F. ; JFA; CORA, Blaton, N., Naesens, L., Balzarini, J., Augustijns, Patrick; U0004215 ;, Kinget, Renaat; U0016947 ;, ...

The use of X-ray powder diffraction and FT-IR spectroscopy to characterise solid dispersions of UC-781 with PEG 6000 and Gelucire 44/14 (2000)

Damian, F. ; JFA; CORA, Blaton, N., Naesens, L., Balzarini, J., Augustijns, Patrick; U0004215 ;, Kinget, Renaat; U0016947 ;, ...

The properties of solid dispersions of the antiviral agent UC-781 in PVP K30 and characterisation of its single crystal structure (2000)

Damian, F. ; JFA; CORA, Blaton, Norbert; U0008061 ;, Naesens, L., Balzarini, J., Augustijns, Patrick; U0004215 ;, Kinget, Renaat; U0016947 ;, ...

Optimization of experimental conditions to study intestinal transport of the antiviral agent UC-781 (2000)

Deferme, S. ; JFA; CORA, Van Gelder, J., De Buck, S., Van Den Mooter, Guy; U0006817 ;, Balzarini, J., Naesens, L., ...

Bicyclams, selective antagonists of the human chemokine receptor CXCR4, potently inhibit feline immunodeficiency virus replication (1999)

Horzinek, M.C., Egberink, H.F., Clercq, E. De, Vliet, A.L.W. Van, Balzarini, J., Bridger, G.J., ...

Bicyclams are low-molecular-weight anti-human immunodeficiency virus (HIV) agents that have been shown to act as potent and selective CXC chemokine receptor 4 (CXCR4) antagonists. Here, we...

Physicochemical characterisation of solid dispersions of UC-781 with PEG 6000 and Gelucire 44/14 (1999)

Damian, F. ; JFA; CORA, Van Den Mooter, Guy; U0006817 ;, Augustijns, Patrick; U0004215 ;, Naesens, L., Balzarini, J., Blaton, Norbert; U0008061 ;, ...

Stability of UC-781 in intestinal homogenates of the rat, rabbit and pig (1998)

Van Den Mooter, Guy; U0006817 JFA; CORA, Stas, G., Damian, F., Augustijns, Patrick; U0004215 ;, Naesens, L., Balzarini, J., ...

Study of the metabolism of UC-781 in intestinal homogenates of the rat, rabbit and pig (1998)

Van Den Mooter, Guy; U0006817 JFA; CORA, Stas, G., Damian, F., Augustijns, Patrick; U0004215 ;, Naesens, L., Balzarini, J., ...

The influence of Gelucire 44/14, PEG 44/14, PEG 6000 and PVP K30 on the dissolution of UC-781 (1998)

Damian, F. ; JFA; CORA, Augustijns, Patrick; U0004215 ;, Naesens, L., Balzarini, J., Kinget, Renaat; U0016947 ;, Van Den Mooter, Guy; U0006817 ;

Antiviral and tumor cell antiproliferative SAR studies on tetracyclic eudistomins .2 (1997)

Kruse, C.G., Balzarini, J., DeClercq, E., Scheeren, H.W., VanMaarseveen, J.H.

Synthesis, conformational analysis and biological evaluation of 2-(5-deoxy-beta-D-ribofuranosyl)pyridine-4-carboxamide. (1996)

JOOS, PE, DEGROOT, A, ESMANS, EL, ALDERWEIRELDT, FC, De Bruyn, André, BALZARINI, J, ...

Synthesis, conformation analysis and biological evaluation of 2-(2,3-dideoxy-beta-D-ribofuranosyl)pyridine-4-carboxamide. (1996)

JOOS, PE, ESMANS, EL, ALDERWEIRELDT, FC, De Bruyn, André, BALZARINI, J, DECLERCQ, E

A two plasmid co-expression system in Escherichia coli for the production of virion-like reverse transcriptase of the human immunodeficiency virus type 1. (1996)

JONCKHEERE, H, DEVREESE, K, DEBYSER, Z, Vandekerckhove, Joël, BALZARINI, J, DESMYTER, J, ...

(R) 9-(2-phosphonylmethoxypropyl) 2,6-diaminopurine is a potent inhibitor of feline immunodeficiency virus infection (1995)

Horzinek, M.C., Vahlenkamp, T.W., Ronde, A. De, Balzarini, J., Naesens, L., Clercq, E. De, ...

Inhibitory effects of acyclic nucleoside phosphonates on human hepatitis B virus and duck hepatitis B virus infections in tissue culture (1994)

Heijtink, R.A., Kruining, J., Wilde, G.A. De, Balzarini, J., Clercq, E. De, Schalm, S.W.

The inhibitory effects of the 9-(2-phosphonylmethoxyethyl)adenine-related compounds (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)-adenine, (S)-9-(3-fluoro-2-phosphonylmethoxypropyl)adenine,...

Meningoradiculoneuritis due to acyclovir-resistant varicella-zostervirus in an acquired-immune-deficiency-syndrome patient (1994)

Snoeck, R., Gérard, M., Sadzot-Delvaux, Catherine, Andrei, G., Balzarini, J., Reymen, D., ...

Varicella zoster virus (VZV) is recognized as one of the major viral pathogens reactivated in patients with the acquired immune deficiency syndrome (AIDS). We report the case of...

Successful treatment of progressive mucocutaneous infection due to acyclovir- and foscarnet-resistant herpes simplex virus with (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC). (1994)

Snoeck, R, Andrei, G, Gerard, Marie-Christine, Silverman, A, Hedderman, A, Balzarini, J, ...

The acyclic nucleoside phosphonate (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) was used topically for the treatment of persistent mucocutaneous infections in two cases. One patient...

Meningoradiculoneuritis due to acyclovir-resistant varicella-zoster virus in a patient with aids (1993)

Snoeck, R., Gerard, M., Sadzot-Delvaux, Catherine, Andrei, G., Balzarini, J., Reymen, D., ...

A new class of HIV-1-specific 6-substituted acyclouridine derivatives: synthesis and anti-HIV-1 activity of 5- or 6-substituted analogues of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) (1991)

Tanaka, H ; JFA; CORA, Baba, M, Hayakawa, H, Sakamaki, T, Miyasaka, T, Ubasawa, M, ...

Suppression of feline immunodeficiency virus infection in vivo by 9-(2-phosphonomethoxyethyl)adenine (1990)

Horzinek, M.C., Egberink, H.F., Borst, M., Niphuis, H., Balzarini, J., Neu, H., ...

The acyclic purine nucleoside analogue 9-(2-phosphonomethoxyethyl)adenine [PMEA; formerly referred to as 9-(2-phosphonylmethoxyethyl)adenine] is a potent and selective inhibitor of human...

Synthesis of 3'-azido-2,3-dideoxynucleosides and 3'-fluoro-2',3'-dideoxynucleosides with a purine base and determination of their anti-hiv activity (1988)

Vanderhaeghe, Hubert; U0007767 ;, Herdewijn, Piet; U0010383 ;, Balzarini, J, De Clercq, Erik; U0003934 ;

3'-fluoro-azido-substituted and 3'-azido-substituted pyrimidine 2',3'-dideoxynucleoside derivatives are potent anti-retrovirus agents (1988)

Balzarini, J, Baba, M, Pauwels, R, Herdewijn, Piet; U0010383, Declercq, E

Effect of (E)-5-(2-bromovinyl)uracil on the catabolism and antitumor activity of 5-fluorouracil in rats and leukemic mice (1986)

Desgranges, C ; JFA; CORA, Razaka, G, De Clercq, Erik; U0003934 ;, Herdewijn, Piet; U0010383 ;, Balzarini, J, Drouillet, F, ...

In contrast to thymine and 5-fluorouracil (FUra) which were cleared from the bloodstream within 2-4 h after their i.p. administration (200 mumol/kg) to rat, (E)-5-(2-bromovinyl)uracil (BVUra)...

Synthesis and biological properties of 2'-deoxy-5-vinyluridine and 2'-deoxy-5-vinylcytidine (1982)

Rahim, S.G., Duggan, M.J.H., Walker, R.T., Jones, A.S., Dyer, R.L., Balzarini, J., ...

Rapid and efficient syntheses for the preparation of 2′-deoxy-5-vinyluridine and 2′-deoxy-5-vinylcytidine are described starting from nucleoside precursors. Contrary to some previous reports,...

Mechanism of anti-HIV action of masked alaninyl d4T-MP derivatives.

Balzarini, J, Karlsson, A, Aquaro, S, Perno, C F, Cahard, D, Naesens, L, ...

So324 is a 2',3'-dideoxy-2',3'-didehydrothymidine-5'-monophosphate (d4T-MP) prodrug containing at the phosphate moiety a phenyl group and the methylester of alanine linked to the phosphate through a...

Suppression of the breakthrough of human immunodeficiency virus type 1 (HIV-1) in cell culture by thiocarboxanilide derivatives when used individually or in combination with other HIV-1-specific inhibitors (i.e., TSAO derivatives).

Balzarini, J, Pérez-Pérez, M J, Vélazquez, S, San-Félix, A, Camarasa, M J, De Clercq, E, ...

Five structurally related thiophene and furane analogues of the oxathiin carboxanilide derivative NSC 615985 (UC84) (designated UC10, UC68, UC81, UC42, and UC16) were identified as potent inhibitors...

Inhibitory effect of 9-(2-phosphonylmethoxyethyl)adenine on visna virus infection in lambs: a model for in vivo testing of candidate anti-human immunodeficiency virus drugs.

Thormar, H, Georgsson, G, Pálsson, P A, Balzarini, J, Naesens, L, Torsteinsdóttir, S, ...

The acyclic nucleoside phosphonate analog 9-(2-phosphonylmethoxyethyl)adenine (PMEA) was recently found to be effective as an inhibitor of visna virus replication and cytopathic effect in sheep...

Human immunodeficiency virus 1 (HIV-1)-specific reverse transcriptase (RT) inhibitors may suppress the replication of specific drug-resistant (E138K)RT HIV-1 mutants or select for highly resistant (Y181C-->C181I)RT HIV-1 mutants.

Balzarini, J, Karlsson, A, Sardana, V V, Emini, E A, Camarasa, M J, De Clercq, E

Mutant HIV-1 that expresses a Glu138-->Lys substitution in its RT [(E138K)RT] is resistant to the HIV-1-specific RT inhibitor 2',5'-bis-O-(tert-butyldimethylsilyl)-3'-spiro-5"-(4"-amino-1",2"-...

Human immunodeficiency virus type 1 (HIV-1) strains selected for resistance against the HIV-1-specific [2',5'-bis-O-(tert-butyldimethylsilyl)-3'-spiro- 5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide)]-beta-D-pentofurano syl (TSAO) nucleoside analogues retain sensitivity to HIV-1-specific nonnucleoside inhibitors.

Balzarini, J, Karlsson, A, Vandamme, A M, Pérez-Pérez, M J, Zhang, H, Vrang, L, ...

We recently reported that a newly discovered class of nucleoside analogues--[2',5'-bis-O-(tert-butyldimethylsilyl)- 3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide)]-beta-D - pentofuranosyl...

2',5'-Bis-O-(tert-butyldimethylsilyl)-3'-spiro-5''-(4''-amino-1'',2''- oxathiole-2'',2'-dioxide)pyrimidine (TSAO) nucleoside analogues: highlyselective inhibitors of human immunodeficiency virus type 1 that are targeted at the viral reverse transcriptase.

Balzarini, J, Pérez-Pérez, M J, San-Félix, A, Schols, D, Perno, C F, Vandamme, A M, ...

A series of pyrimidine nucleoside analogues containing [2',5'-bis-O-(tert-butyldimethylsilyl)-3'-spiro-5''-(4''-amino- 1'',2''-oxathiole-2'',2''-dioxide)]-beta-D-ribofuranose as the pentose were...

Potent and selective inhibition of human immunodeficiency virus (HIV)-1 and HIV-2 replication by a class of bicyclams interacting with a viral uncoating event.

De Clercq, E, Yamamoto, N, Pauwels, R, Baba, M, Schols, D, Nakashima, H, ...

A series of bicyclams have been shown to be potent and selective inhibitors of human immunodeficiency virus (HIV). The compounds are inhibitory to the replication of various HIV-1 and HIV-2 strains...

Intracellular metabolism and mechanism of anti-retrovirus action of 9-(2-phosphonylmethoxyethyl)adenine, a potent anti-human immunodeficiency virus compound.

Balzarini, J, Hao, Z, Herdewijn, P, Johns, D G, De Clercq, E

9-(2-Phosphonylmethoxyethyl)adenine (PMEA) is a potent and selective inhibitor of retrovirus (i.e., human immunodeficiency virus) replication in vitro and in vivo. Uptake of PMEA by human MT-4 cells...

9-[(2RS)-3-fluoro-2-phosphonylmethoxypropyl] derivatives of purines: a class of highly selective antiretroviral agents in vitro and in vivo.

Balzarini, J, Holy, A, Jindrich, J, Dvorakova, H, Hao, Z, Snoeck, R, ...

A new class of compounds, 9-[(2RS)-3-fluoro-2-phosphonylmethoxypropyl] [(RS)-FPMP] derivatives of purines, is described that has selective activity against a broad spectrum of retroviruses [including...

Suppression of feline immunodeficiency virus infection in vivo by 9-(2-phosphonomethoxyethyl)adenine.

Egberink, H, Borst, M, Niphuis, H, Balzarini, J, Neu, H, Schellekens, H, ...

The acyclic purine nucleoside analogue 9-(2-phosphonomethoxyethyl)adenine [PMEA; formerly referred to as 9-(2-phosphonylmethoxyethyl)adenine] is a potent and selective inhibitor of human...

1,1,3-Trioxo-2H,4H-Thieno[3,4-e][1,2,4]Thiadiazine (TTD) Derivatives: a New Class of Nonnucleoside Human Immunodeficiency Virus Type 1 (HIV-1) Reverse Transcriptase Inhibitors with Anti-HIV-1 Activity

Witvrouw, M., Arranz, M. E., Pannecouque, C., Declercq, R., Jonckheere, H., Schmit, J.-C., ...

We report the development of a new group of nonnucleoside reverse transcriptase inhibitors (NNRTIs). One of the most active congeners of this series of...

Antiretrovirus Activity of a Novel Class of Acyclic Pyrimidine Nucleoside Phosphonates†

Balzarini, J., Pannecouque, C., De Clercq, E., Aquaro, S., Perno, C.-F., Egberink, H., ...

A novel class of acyclic nucleoside phosphonates has been discovered in which the base consists of a pyrimidine preferably containing an amino group at C-2 and C-4 and a 2-(phosphonomethoxy)ethoxy...

(R)-9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine is a potent inhibitor of feline immunodeficiency virus infection.

Vahlenkamp, T W, De Ronde, A, Balzarini, J, Naesens, L, De Clercq, E, Van Eijk, M J, ...

The antiviral efficacy of acyclic nucleoside phosphonates, including 9-(2-phosphonylmethoxyethyl)adenine (PMEA) and (R)-9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine [(R)-PMPDAP] against feline...

Differential activities of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine derivatives against different human immunodeficiency virus type 1 mutant strains.

Balzarini, J, Baba, M, De Clercq, E

A series of 23 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine derivatives that were highly potent inhibitors of wild-type human immunodeficiency virus type 1 strain IIIB (HIV-1/IIIB) replication...

Antiretroviral activity and pharmacokinetics in mice of oral bis(pivaloyloxymethyl)-9-(2-phosphonylmethoxyethyl)adenine, the bis(pivaloyloxymethyl) ester prodrug of 9-(2-phosphonylmethoxyethyl)adenine.

Naesens, L, Balzarini, J, Bischofberger, N, De Clercq, E

Lipophilic ester prodrugs of 9-(2-phosphonylmethoxyethyl)adenine (PMEA), i.e., bis(pivaloyloxymethyl)-PMEA [bis(POM)-PMEA] and diphenyl-PMEA, have been synthesized in an attempt to increase the oral...

Identification of novel thiocarboxanilide derivatives that suppress a variety of drug-resistant mutant human immunodeficiency virus type 1 strains at a potency similar to that for wild-type virus.

Balzarini, J, Brouwer, W G, Dao, D C, Osika, E M, De Clercq, E

A large variety of carboxanilide and thiocarboxanilide derivatives in which the original oxathiin or aliphatic moieties present in the prototype compounds UC84 and UC38 were replaced by an (un)...

SRR-SB3, a disulfide-containing macrolide that inhibits a late stage of the replicative cycle of human immunodeficiency virus.

Witvrouw, M, Balzarini, J, Pannecouque, C, Jhaumeer-Laulloo, S, Esté, J A, Schols, D, ...

From a series of macrocyclic diamides possessing the disulfide linkage, only SRR-SB3, a compound that complexes with zinc, was found to inhibit human immunodeficiency virus type 1 (HIV-1; strain...

Antiretroviral activities of acyclic nucleoside phosphonates [9-(2-phosphonylmethoxyethyl)adenine, 9-(2-phosphonylmethoxyethyl)guanine, (R)-9-(2-phosphonylmethoxypropyl)adenine, and MDL 74,968] in cell cultures and murine sarcoma virus-infected newborn NMRI mice.

Balzarini, J, Vahlenkamp, T, Egberink, H, Hartmann, K, Witvrouw, M, Pannecouque, C, ...

From a side-by-side comparative study, the acyclic nucleoside phosphonates (R)-9-(2-phosphonylmethoxypropyl)adenine [(R)-PMPA] and 9-(2-methylidene-3-phosphonomethoxypropyl)guanine (MDL 74,968)...

Phosphonylmethoxyethyl purine derivatives, a new class of anti-human immunodeficiency virus agents.

Pauwels, R, Balzarini, J, Schols, D, Baba, M, Desmyter, J, Rosenberg, I, ...

A study of the structure-activity relationship of a series of newly synthesized phosphonylmethoxyalkyl purine and pyrimidine derivatives revealed that several adenine derivatives substituted at the...

Broad-spectrum antiviral activities of neplanocin A, 3-deazaneplanocin A, and their 5'-nor derivatives.

De Clercq, E, Cools, M, Balzarini, J, Marquez, V E, Borcherding, D R, Borchardt, R T, ...

The neplanocin A analogs, 3-deazaneplanocin A, 9-(trans-2',trans-3'-dihydroxycyclopent-4'-enyl)adenine (DHCA), and 9-(trans-2',trans-3'-dihydroxycyclopent-4'-enyl)-3-deazaadenine (DHCDA), all potent...

9-(2-Phosphonylmethoxyethyl)adenine in the treatment of murine acquired immunodeficiency disease and opportunistic herpes simplex virus infections.

Gangemi, J D, Cozens, R M, De Clercq, E, Balzarini, J, Hochkeppel, H K

The murine model of acquired immunodeficiency disease was used to evaluate both the antiretroviral and antiherpetic activities of the acyclic nucleotide analog 9-(2-phosphonylmethoxyethyl)adenine...

Ribavirin antagonizes inhibitory effects of pyrimidine 2',3'-dideoxynucleosides but enhances inhibitory effects of purine 2',3'-dideoxynucleosides on replication of human immunodeficiency virus in vitro.

Baba, M, Pauwels, R, Balzarini, J, Herdewijn, P, De Clercq, E, Desmyter, J

The combined antiviral effects of various 2',3'-dideoxynucleosides and ribavirin on the replication of human immunodeficiency virus type 1 in MT-4 cells have been examined. Ribavirin antagonized the...

Differential antiherpesvirus and antiretrovirus effects of the (S) and (R) enantiomers of acyclic nucleoside phosphonates: potent and selective in vitro and in vivo antiretrovirus activities of (R)-9-(2-phosphonomethoxypropyl)-2,6-diaminopurine.

Balzarini, J, Holy, A, Jindrich, J, Naesens, L, Snoeck, R, Schols, D, ...

The (S)- and (R)-enantiomers of acyclic purine nucleoside phosphonate analogs (i.e., 3-hydroxy-2-phosphonomethoxypropyl [HPMP] derivatives, 3-fluoro-2-phosphonomethoxypropyl [FPMP] derivatives, and...

The N-7-substituted acyclic nucleoside analog 2-amino-7-[(1,3-dihydroxy-2-propoxy)methyl]purine is a potent and selective inhibitor of herpesvirus replication.

Neyts, J, Andrei, G, Snoeck, R, Jähne, G, Winkler, I, Helsberg, M, ...

2-Amino-7-[(1,3-dihydroxy-2-propoxy)methyl]purine (compound S2242) represents the first antivirally active nucleoside analog with the side chain attached to the N-7 position of the purine ring....

[2',5'-Bis-O-(tert-butyldimethylsilyl)]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide) (TSAO) derivatives of purine and pyrimidinenucleosides as potent and selective inhibitors of human immunodeficiency virus type 1.

Balzarini, J, Pérez-Pérez, M J, San-Félix, A, Velazquez, S, Camarasa, M J, De Clercq, E

The [2',5'-bis-O-(tert-butyldimethylsilyl)]-3'-spiro-5''-(4''-amino- 1'',2''-oxathiole-2'',2''-dioxide) (TSAO) derivatives of ribofuranosylthymine, uridine, 5-bromouridine, 5-methylcytidine, inosine,...

Characteristics of the Pro225His mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase that appears under selective pressure of dose-escalating quinoxaline treatment of HIV-1.

Pelemans, H, Esnouf, R, Dunkler, A, Parniak, M A, Vandamme, A M, Karlsson, A, ...

Treatment of human immunodeficiency virus type 1 (HIV-1)-infected CEM cell cultures with escalating concentrations of the quinoxaline S-2720 resulted in an ordered appearance of single and multiple...

Inhibition of visna virus replication by 2',3'-dideoxynucleosides and acyclic nucleoside phosphonate analogs.

Thormar, H, Balzarini, J, Holy, A, Jindrich, J, Rosenberg, I, Debyser, Z, ...

A series of acyclic nucleoside phosphonate (ANP) and 2',3'-dideoxynucleoside (ddN) derivatives were evaluated for their inhibitory effects on visna virus replication and maedi/visna virus-induced...

Resistance pattern of human immunodeficiency virus type 1 reverse transcriptase to quinoxaline S-2720.

Balzarini, J, Karlsson, A, Meichsner, C, Paessens, A, Riess, G, De Clercq, E, ...

The human immunodeficiency virus type 1 (HIV-1)-specific reverse transcriptase (RT) inhibitor quinoxaline S-2720 showed a more-potent inhibitory effect on HIV-1-induced cytopathicity in CEM cells...

Treatment of human immunodeficiency virus type 1 (HIV-1)-infected cells with combinations of HIV-1-specific inhibitors results in a different resistance pattern than does treatment with single-drug therapy.

Balzarini, J, Karlsson, A, Pérez-Pérez, M J, Camarasa, M J, Tarpley, W G, De Clercq, E

Human immunodeficiency virus type 1 (HIV-1)-infected CEM cells were treated by the HIV-1-specific inhibitors bis-heteroarylpiperazine (BHAP),...

Alpha-(1-3)- and alpha-(1-6)-D-mannose-specific plant lectins are markedly inhibitory to human immunodeficiency virus and cytomegalovirus infections in vitro.

Balzarini, J, Schols, D, Neyts, J, Van Damme, E, Peumans, W, De Clercq, E

The alpha-(1-3)-D-mannose- and alpha-(1-6)-D-mannose-specific agglutinins (lectins) from Galanthus nivalis, Hippeastrum hybrid, Narcissus pseudonarcissus, and Listera ovata inhibited infection of...

Antiviral activities of 5-ethynyl-1-beta-D-ribofuranosylimidazole-4- carboxamide and related compounds.

De Clercq, E, Cools, M, Balzarini, J, Snoeck, R, Andrei, G, Hosoya, M, ...

A series of novel compounds, 5-alkynyl-1-beta-D-ribofuranosylimidazole-4- carboxamides, have been identified as broad-spectrum antiviral agents. 5-Ethynyl-1-beta-D-ribofuranosylimidazole-4-...

Differential inhibitory effects of sulfated polysaccharides and polymers on the replication of various myxoviruses and retroviruses, depending on the composition of the target amino acid sequences of the viral envelope glycoproteins.

Hosoya, M, Balzarini, J, Shigeta, S, De Clercq, E

Sulfated polysaccharides (i.e., dextran sulfate) and sulfated polymers (i.e., sulfated polyvinylalcohol and sulfated copolymers of acrylic acid with vinylalcohol) were found to be potent and...

Mechanism of inhibitory effect of dextran sulfate and heparin on replication of human immunodeficiency virus in vitro.

Baba, M, Pauwels, R, Balzarini, J, Arnout, J, Desmyter, J, De Clercq, E

The sulfated polysaccharides dextran sulfate and heparin have proved to be potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) in vitro. Dextran sulfate (Mr 5000) and...

Highly potent and selective inhibition of human immunodeficiency virus by the bicyclam derivative JM3100.

De Clercq, E, Yamamoto, N, Pauwels, R, Balzarini, J, Witvrouw, M, De Vreese, K, ...

Bicyclams, in which the cyclam (1,4,8,11-tetraazacyclotetradecane) moieties are tethered via an aliphatic bridge (i.e., propylene, as in JM2763) are potent and selective inhibitors of human...

Inhibitory effects of acyclic nucleoside phosphonates on human hepatitis B virus and duck hepatitis B virus infections in tissue culture.

Heijtink, R A, Kruining, J, De Wilde, G A, Balzarini, J, De Clercq, E, Schalm, S W

The inhibitory effects of the 9-(2-phosphonylmethoxyethyl)adenine-related compounds (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)-adenine, (S)-9-(3-fluoro-2-phosphonylmethoxypropyl)adenine,...

Marked in vivo antiretrovirus activity of 9-(2-phosphonylmethoxyethyl)adenine, a selective anti-human immunodeficiency virus agent.

Balzarini, J, Naesens, L, Herdewijn, P, Rosenberg, I, Holy, A, Pauwels, R, ...

9-(2-Phosphonylmethoxyethyl)adenine (PMEA) is a potent and selective inhibitor of the replication of human immunodeficiency virus (HIV) in vitro in human T-lymphocyte MT-4, H9, and ATH8 cells. PMEA...

Synthesis and biological properties of 2'-deoxy-5-vinyluridine and 2'deoxy-5-vinylcytidine.

Rahim, S G, Duggan, M J, Walker, R T, Jones, A S, Dyer, R L, Balzarini, J, ...

Rapid and efficient syntheses for the preparation of 2'-deoxy-5-vinyluridine and 2'-deoxy-5-vinylcytidine are described starting from nucleoside precursors. Contrary to some previous reports,...

Assay method for monitoring the inhibitory effects of antimetabolites on the activity of inosinate dehydrogenase in intact human CEM lymphocytes.

Balzarini, J, De Clercq, E

A rapid and convenient method has been developed to monitor the inhibition of inosinate (IMP) dehydrogenase by antimetabolites in intact human CEM lymphocytes. This method is based on the...

Thymidylate synthetase-deficient mouse FM3A mammary carcinoma cell line as a tool for studying the thymidine salvage pathway and the incorporation of thymidine analogues into host cell DNA.

Balzarini, J, De Clercq, E, Ayusawa, D, Seno, T

A thymidylate (dTMP) synthetase-deficient murine mammary carcinoma cell line (FM3A/TS-), auxotrophic for thymidine (dThd), proved extremely useful for studying the dependence of cell growth on the...

Antiviral activity of the 3'-amino derivative of (E)-5-(2-bromovinyl)-2'-deoxyuridine.

De Clercq, E, Descamps, J, Balzarini, J, Fukui, T, Allaudeen, H S

3'-NH2-BV-dUrd, the 3'-amino derivative of (E)-5-(2-bromovinyl)-2'-deoxyuridine, was found to be a potent and selective inhibitor of herpes simplex virus type 1 (HSV-1) and varicella-zoster virus...

Novel ribofuranosylnucleoside lead compounds for potent and selective inhibitors of mitochondrial thymidine kinase-2.

Balzarini, J, Zhu, C, De Clercq , E, Pérez-Pérez, M J, Chamorro, C, Camarasa, M J, ...

The ribonucleoside analogues (E)-5-(2-bromovinyl)uridine (5-BV-Urd) and 3'-spiro-(4'-amino-1',2'-oxathiole-2',2'-dioxide)-5-methyluridine (3'-AOD-5-MeUrd) emerged as potent and selective competitive...

Anti-(herpes simplex virus) activity of 4'-thio-2'-deoxyuridines: a biochemical investigation for viral and cellular target enzymes.

Verri, A, Focher, F, Duncombe, R J, Basnak, I, Walker, R T, Coe, P L, ...

The antiviral activity of several nucleoside analogues is often limited by their rapid degradation by pyrimidine nucleoside phosphorylases. In an attempt to avoid this degradation, several modified...

Mechanism of anti-HIV action of masked alaninyl d4T-MP derivatives.

Balzarini, J, Karlsson, A, Aquaro, S, Perno, C F, Cahard, D, Naesens, L, ...

So324 is a 2',3'-dideoxy-2',3'-didehydrothymidine-5'-monophosphate (d4T-MP) prodrug containing at the phosphate moiety a phenyl group and the methylester of alanine linked to the phosphate through a...

Suppression of the breakthrough of human immunodeficiency virus type 1 (HIV-1) in cell culture by thiocarboxanilide derivatives when used individually or in combination with other HIV-1-specific inhibitors (i.e., TSAO derivatives).

Balzarini, J, Pérez-Pérez, M J, Vélazquez, S, San-Félix, A, Camarasa, M J, De Clercq, E, ...

Five structurally related thiophene and furane analogues of the oxathiin carboxanilide derivative NSC 615985 (UC84) (designated UC10, UC68, UC81, UC42, and UC16) were identified as potent inhibitors...

Inhibitory effect of 9-(2-phosphonylmethoxyethyl)adenine on visna virus infection in lambs: a model for in vivo testing of candidate anti-human immunodeficiency virus drugs.

Thormar, H, Georgsson, G, Pálsson, P A, Balzarini, J, Naesens, L, Torsteinsdóttir, S, ...

The acyclic nucleoside phosphonate analog 9-(2-phosphonylmethoxyethyl)adenine (PMEA) was recently found to be effective as an inhibitor of visna virus replication and cytopathic effect in sheep...

Human immunodeficiency virus 1 (HIV-1)-specific reverse transcriptase (RT) inhibitors may suppress the replication of specific drug-resistant (E138K)RT HIV-1 mutants or select for highly resistant (Y181C-->C181I)RT HIV-1 mutants.

Balzarini, J, Karlsson, A, Sardana, V V, Emini, E A, Camarasa, M J, De Clercq, E

Mutant HIV-1 that expresses a Glu138-->Lys substitution in its RT [(E138K)RT] is resistant to the HIV-1-specific RT inhibitor 2',5'-bis-O-(tert-butyldimethylsilyl)-3'-spiro-5"-(4"-amino-1",2"-...

Human immunodeficiency virus type 1 (HIV-1) strains selected for resistance against the HIV-1-specific [2',5'-bis-O-(tert-butyldimethylsilyl)-3'-spiro- 5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide)]-beta-D-pentofurano syl (TSAO) nucleoside analogues retain sensitivity to HIV-1-specific nonnucleoside inhibitors.

Balzarini, J, Karlsson, A, Vandamme, A M, Pérez-Pérez, M J, Zhang, H, Vrang, L, ...

We recently reported that a newly discovered class of nucleoside analogues--[2',5'-bis-O-(tert-butyldimethylsilyl)- 3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide)]-beta-D - pentofuranosyl...

2',5'-Bis-O-(tert-butyldimethylsilyl)-3'-spiro-5''-(4''-amino-1'',2''- oxathiole-2'',2'-dioxide)pyrimidine (TSAO) nucleoside analogues: highlyselective inhibitors of human immunodeficiency virus type 1 that are targeted at the viral reverse transcriptase.

Balzarini, J, Pérez-Pérez, M J, San-Félix, A, Schols, D, Perno, C F, Vandamme, A M, ...

A series of pyrimidine nucleoside analogues containing [2',5'-bis-O-(tert-butyldimethylsilyl)-3'-spiro-5''-(4''-amino- 1'',2''-oxathiole-2'',2''-dioxide)]-beta-D-ribofuranose as the pentose were...

Potent and selective inhibition of human immunodeficiency virus (HIV)-1 and HIV-2 replication by a class of bicyclams interacting with a viral uncoating event.

De Clercq, E, Yamamoto, N, Pauwels, R, Baba, M, Schols, D, Nakashima, H, ...

A series of bicyclams have been shown to be potent and selective inhibitors of human immunodeficiency virus (HIV). The compounds are inhibitory to the replication of various HIV-1 and HIV-2 strains...

Intracellular metabolism and mechanism of anti-retrovirus action of 9-(2-phosphonylmethoxyethyl)adenine, a potent anti-human immunodeficiency virus compound.

Balzarini, J, Hao, Z, Herdewijn, P, Johns, D G, De Clercq, E

9-(2-Phosphonylmethoxyethyl)adenine (PMEA) is a potent and selective inhibitor of retrovirus (i.e., human immunodeficiency virus) replication in vitro and in vivo. Uptake of PMEA by human MT-4 cells...

9-[(2RS)-3-fluoro-2-phosphonylmethoxypropyl] derivatives of purines: a class of highly selective antiretroviral agents in vitro and in vivo.

Balzarini, J, Holy, A, Jindrich, J, Dvorakova, H, Hao, Z, Snoeck, R, ...

A new class of compounds, 9-[(2RS)-3-fluoro-2-phosphonylmethoxypropyl] [(RS)-FPMP] derivatives of purines, is described that has selective activity against a broad spectrum of retroviruses [including...

Suppression of feline immunodeficiency virus infection in vivo by 9-(2-phosphonomethoxyethyl)adenine.

Egberink, H, Borst, M, Niphuis, H, Balzarini, J, Neu, H, Schellekens, H, ...

The acyclic purine nucleoside analogue 9-(2-phosphonomethoxyethyl)adenine [PMEA; formerly referred to as 9-(2-phosphonylmethoxyethyl)adenine] is a potent and selective inhibitor of human...

1,1,3-Trioxo-2H,4H-Thieno[3,4-e][1,2,4]Thiadiazine (TTD) Derivatives: a New Class of Nonnucleoside Human Immunodeficiency Virus Type 1 (HIV-1) Reverse Transcriptase Inhibitors with Anti-HIV-1 Activity

Witvrouw, M., Arranz, M. E., Pannecouque, C., Declercq, R., Jonckheere, H., Schmit, J.-C., ...

We report the development of a new group of nonnucleoside reverse transcriptase inhibitors (NNRTIs). One of the most active congeners of this series of...

Antiretrovirus Activity of a Novel Class of Acyclic Pyrimidine Nucleoside Phosphonates†

Balzarini, J., Pannecouque, C., De Clercq, E., Aquaro, S., Perno, C.-F., Egberink, H., ...

A novel class of acyclic nucleoside phosphonates has been discovered in which the base consists of a pyrimidine preferably containing an amino group at C-2 and C-4 and a 2-(phosphonomethoxy)ethoxy...

(R)-9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine is a potent inhibitor of feline immunodeficiency virus infection.

Vahlenkamp, T W, De Ronde, A, Balzarini, J, Naesens, L, De Clercq, E, Van Eijk, M J, ...

The antiviral efficacy of acyclic nucleoside phosphonates, including 9-(2-phosphonylmethoxyethyl)adenine (PMEA) and (R)-9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine [(R)-PMPDAP] against feline...

Differential activities of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine derivatives against different human immunodeficiency virus type 1 mutant strains.

Balzarini, J, Baba, M, De Clercq, E

A series of 23 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine derivatives that were highly potent inhibitors of wild-type human immunodeficiency virus type 1 strain IIIB (HIV-1/IIIB) replication...

Antiretroviral activity and pharmacokinetics in mice of oral bis(pivaloyloxymethyl)-9-(2-phosphonylmethoxyethyl)adenine, the bis(pivaloyloxymethyl) ester prodrug of 9-(2-phosphonylmethoxyethyl)adenine.

Naesens, L, Balzarini, J, Bischofberger, N, De Clercq, E

Lipophilic ester prodrugs of 9-(2-phosphonylmethoxyethyl)adenine (PMEA), i.e., bis(pivaloyloxymethyl)-PMEA [bis(POM)-PMEA] and diphenyl-PMEA, have been synthesized in an attempt to increase the oral...

Identification of novel thiocarboxanilide derivatives that suppress a variety of drug-resistant mutant human immunodeficiency virus type 1 strains at a potency similar to that for wild-type virus.

Balzarini, J, Brouwer, W G, Dao, D C, Osika, E M, De Clercq, E

A large variety of carboxanilide and thiocarboxanilide derivatives in which the original oxathiin or aliphatic moieties present in the prototype compounds UC84 and UC38 were replaced by an (un)...

SRR-SB3, a disulfide-containing macrolide that inhibits a late stage of the replicative cycle of human immunodeficiency virus.

Witvrouw, M, Balzarini, J, Pannecouque, C, Jhaumeer-Laulloo, S, Esté, J A, Schols, D, ...

From a series of macrocyclic diamides possessing the disulfide linkage, only SRR-SB3, a compound that complexes with zinc, was found to inhibit human immunodeficiency virus type 1 (HIV-1; strain...

Antiretroviral activities of acyclic nucleoside phosphonates [9-(2-phosphonylmethoxyethyl)adenine, 9-(2-phosphonylmethoxyethyl)guanine, (R)-9-(2-phosphonylmethoxypropyl)adenine, and MDL 74,968] in cell cultures and murine sarcoma virus-infected newborn NMRI mice.

Balzarini, J, Vahlenkamp, T, Egberink, H, Hartmann, K, Witvrouw, M, Pannecouque, C, ...

From a side-by-side comparative study, the acyclic nucleoside phosphonates (R)-9-(2-phosphonylmethoxypropyl)adenine [(R)-PMPA] and 9-(2-methylidene-3-phosphonomethoxypropyl)guanine (MDL 74,968)...

Phosphonylmethoxyethyl purine derivatives, a new class of anti-human immunodeficiency virus agents.

Pauwels, R, Balzarini, J, Schols, D, Baba, M, Desmyter, J, Rosenberg, I, ...

A study of the structure-activity relationship of a series of newly synthesized phosphonylmethoxyalkyl purine and pyrimidine derivatives revealed that several adenine derivatives substituted at the...

Broad-spectrum antiviral activities of neplanocin A, 3-deazaneplanocin A, and their 5'-nor derivatives.

De Clercq, E, Cools, M, Balzarini, J, Marquez, V E, Borcherding, D R, Borchardt, R T, ...

The neplanocin A analogs, 3-deazaneplanocin A, 9-(trans-2',trans-3'-dihydroxycyclopent-4'-enyl)adenine (DHCA), and 9-(trans-2',trans-3'-dihydroxycyclopent-4'-enyl)-3-deazaadenine (DHCDA), all potent...

9-(2-Phosphonylmethoxyethyl)adenine in the treatment of murine acquired immunodeficiency disease and opportunistic herpes simplex virus infections.

Gangemi, J D, Cozens, R M, De Clercq, E, Balzarini, J, Hochkeppel, H K

The murine model of acquired immunodeficiency disease was used to evaluate both the antiretroviral and antiherpetic activities of the acyclic nucleotide analog 9-(2-phosphonylmethoxyethyl)adenine...

Ribavirin antagonizes inhibitory effects of pyrimidine 2',3'-dideoxynucleosides but enhances inhibitory effects of purine 2',3'-dideoxynucleosides on replication of human immunodeficiency virus in vitro.

Baba, M, Pauwels, R, Balzarini, J, Herdewijn, P, De Clercq, E, Desmyter, J

The combined antiviral effects of various 2',3'-dideoxynucleosides and ribavirin on the replication of human immunodeficiency virus type 1 in MT-4 cells have been examined. Ribavirin antagonized the...

Differential antiherpesvirus and antiretrovirus effects of the (S) and (R) enantiomers of acyclic nucleoside phosphonates: potent and selective in vitro and in vivo antiretrovirus activities of (R)-9-(2-phosphonomethoxypropyl)-2,6-diaminopurine.

Balzarini, J, Holy, A, Jindrich, J, Naesens, L, Snoeck, R, Schols, D, ...

The (S)- and (R)-enantiomers of acyclic purine nucleoside phosphonate analogs (i.e., 3-hydroxy-2-phosphonomethoxypropyl [HPMP] derivatives, 3-fluoro-2-phosphonomethoxypropyl [FPMP] derivatives, and...

The N-7-substituted acyclic nucleoside analog 2-amino-7-[(1,3-dihydroxy-2-propoxy)methyl]purine is a potent and selective inhibitor of herpesvirus replication.

Neyts, J, Andrei, G, Snoeck, R, Jähne, G, Winkler, I, Helsberg, M, ...

2-Amino-7-[(1,3-dihydroxy-2-propoxy)methyl]purine (compound S2242) represents the first antivirally active nucleoside analog with the side chain attached to the N-7 position of the purine ring....

[2',5'-Bis-O-(tert-butyldimethylsilyl)]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide) (TSAO) derivatives of purine and pyrimidinenucleosides as potent and selective inhibitors of human immunodeficiency virus type 1.

Balzarini, J, Pérez-Pérez, M J, San-Félix, A, Velazquez, S, Camarasa, M J, De Clercq, E

The [2',5'-bis-O-(tert-butyldimethylsilyl)]-3'-spiro-5''-(4''-amino- 1'',2''-oxathiole-2'',2''-dioxide) (TSAO) derivatives of ribofuranosylthymine, uridine, 5-bromouridine, 5-methylcytidine, inosine,...

Characteristics of the Pro225His mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase that appears under selective pressure of dose-escalating quinoxaline treatment of HIV-1.

Pelemans, H, Esnouf, R, Dunkler, A, Parniak, M A, Vandamme, A M, Karlsson, A, ...

Treatment of human immunodeficiency virus type 1 (HIV-1)-infected CEM cell cultures with escalating concentrations of the quinoxaline S-2720 resulted in an ordered appearance of single and multiple...

Inhibition of visna virus replication by 2',3'-dideoxynucleosides and acyclic nucleoside phosphonate analogs.

Thormar, H, Balzarini, J, Holy, A, Jindrich, J, Rosenberg, I, Debyser, Z, ...

A series of acyclic nucleoside phosphonate (ANP) and 2',3'-dideoxynucleoside (ddN) derivatives were evaluated for their inhibitory effects on visna virus replication and maedi/visna virus-induced...

Resistance pattern of human immunodeficiency virus type 1 reverse transcriptase to quinoxaline S-2720.

Balzarini, J, Karlsson, A, Meichsner, C, Paessens, A, Riess, G, De Clercq, E, ...

The human immunodeficiency virus type 1 (HIV-1)-specific reverse transcriptase (RT) inhibitor quinoxaline S-2720 showed a more-potent inhibitory effect on HIV-1-induced cytopathicity in CEM cells...

Treatment of human immunodeficiency virus type 1 (HIV-1)-infected cells with combinations of HIV-1-specific inhibitors results in a different resistance pattern than does treatment with single-drug therapy.

Balzarini, J, Karlsson, A, Pérez-Pérez, M J, Camarasa, M J, Tarpley, W G, De Clercq, E

Human immunodeficiency virus type 1 (HIV-1)-infected CEM cells were treated by the HIV-1-specific inhibitors bis-heteroarylpiperazine (BHAP),...

Alpha-(1-3)- and alpha-(1-6)-D-mannose-specific plant lectins are markedly inhibitory to human immunodeficiency virus and cytomegalovirus infections in vitro.

Balzarini, J, Schols, D, Neyts, J, Van Damme, E, Peumans, W, De Clercq, E

The alpha-(1-3)-D-mannose- and alpha-(1-6)-D-mannose-specific agglutinins (lectins) from Galanthus nivalis, Hippeastrum hybrid, Narcissus pseudonarcissus, and Listera ovata inhibited infection of...

Antiviral activities of 5-ethynyl-1-beta-D-ribofuranosylimidazole-4- carboxamide and related compounds.

De Clercq, E, Cools, M, Balzarini, J, Snoeck, R, Andrei, G, Hosoya, M, ...

A series of novel compounds, 5-alkynyl-1-beta-D-ribofuranosylimidazole-4- carboxamides, have been identified as broad-spectrum antiviral agents. 5-Ethynyl-1-beta-D-ribofuranosylimidazole-4-...

Differential inhibitory effects of sulfated polysaccharides and polymers on the replication of various myxoviruses and retroviruses, depending on the composition of the target amino acid sequences of the viral envelope glycoproteins.

Hosoya, M, Balzarini, J, Shigeta, S, De Clercq, E

Sulfated polysaccharides (i.e., dextran sulfate) and sulfated polymers (i.e., sulfated polyvinylalcohol and sulfated copolymers of acrylic acid with vinylalcohol) were found to be potent and...

Mechanism of inhibitory effect of dextran sulfate and heparin on replication of human immunodeficiency virus in vitro.

Baba, M, Pauwels, R, Balzarini, J, Arnout, J, Desmyter, J, De Clercq, E

The sulfated polysaccharides dextran sulfate and heparin have proved to be potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) in vitro. Dextran sulfate (Mr 5000) and...

Highly potent and selective inhibition of human immunodeficiency virus by the bicyclam derivative JM3100.

De Clercq, E, Yamamoto, N, Pauwels, R, Balzarini, J, Witvrouw, M, De Vreese, K, ...

Bicyclams, in which the cyclam (1,4,8,11-tetraazacyclotetradecane) moieties are tethered via an aliphatic bridge (i.e., propylene, as in JM2763) are potent and selective inhibitors of human...

Inhibitory effects of acyclic nucleoside phosphonates on human hepatitis B virus and duck hepatitis B virus infections in tissue culture.

Heijtink, R A, Kruining, J, De Wilde, G A, Balzarini, J, De Clercq, E, Schalm, S W

The inhibitory effects of the 9-(2-phosphonylmethoxyethyl)adenine-related compounds (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)-adenine, (S)-9-(3-fluoro-2-phosphonylmethoxypropyl)adenine,...

Marked in vivo antiretrovirus activity of 9-(2-phosphonylmethoxyethyl)adenine, a selective anti-human immunodeficiency virus agent.

Balzarini, J, Naesens, L, Herdewijn, P, Rosenberg, I, Holy, A, Pauwels, R, ...

9-(2-Phosphonylmethoxyethyl)adenine (PMEA) is a potent and selective inhibitor of the replication of human immunodeficiency virus (HIV) in vitro in human T-lymphocyte MT-4, H9, and ATH8 cells. PMEA...

Synthesis and biological properties of 2'-deoxy-5-vinyluridine and 2'deoxy-5-vinylcytidine.

Rahim, S G, Duggan, M J, Walker, R T, Jones, A S, Dyer, R L, Balzarini, J, ...

Rapid and efficient syntheses for the preparation of 2'-deoxy-5-vinyluridine and 2'-deoxy-5-vinylcytidine are described starting from nucleoside precursors. Contrary to some previous reports,...

Assay method for monitoring the inhibitory effects of antimetabolites on the activity of inosinate dehydrogenase in intact human CEM lymphocytes.

Balzarini, J, De Clercq, E

A rapid and convenient method has been developed to monitor the inhibition of inosinate (IMP) dehydrogenase by antimetabolites in intact human CEM lymphocytes. This method is based on the...

Thymidylate synthetase-deficient mouse FM3A mammary carcinoma cell line as a tool for studying the thymidine salvage pathway and the incorporation of thymidine analogues into host cell DNA.

Balzarini, J, De Clercq, E, Ayusawa, D, Seno, T

A thymidylate (dTMP) synthetase-deficient murine mammary carcinoma cell line (FM3A/TS-), auxotrophic for thymidine (dThd), proved extremely useful for studying the dependence of cell growth on the...

Antiviral activity of the 3'-amino derivative of (E)-5-(2-bromovinyl)-2'-deoxyuridine.

De Clercq, E, Descamps, J, Balzarini, J, Fukui, T, Allaudeen, H S

3'-NH2-BV-dUrd, the 3'-amino derivative of (E)-5-(2-bromovinyl)-2'-deoxyuridine, was found to be a potent and selective inhibitor of herpes simplex virus type 1 (HSV-1) and varicella-zoster virus...

Novel ribofuranosylnucleoside lead compounds for potent and selective inhibitors of mitochondrial thymidine kinase-2.

Balzarini, J, Zhu, C, De Clercq , E, Pérez-Pérez, M J, Chamorro, C, Camarasa, M J, ...

The ribonucleoside analogues (E)-5-(2-bromovinyl)uridine (5-BV-Urd) and 3'-spiro-(4'-amino-1',2'-oxathiole-2',2'-dioxide)-5-methyluridine (3'-AOD-5-MeUrd) emerged as potent and selective competitive...

Anti-(herpes simplex virus) activity of 4'-thio-2'-deoxyuridines: a biochemical investigation for viral and cellular target enzymes.

Verri, A, Focher, F, Duncombe, R J, Basnak, I, Walker, R T, Coe, P L, ...

The antiviral activity of several nucleoside analogues is often limited by their rapid degradation by pyrimidine nucleoside phosphorylases. In an attempt to avoid this degradation, several modified...

Synthesis, Characterization and Antiviral Properties of Pd(II) Complexes With Penciclovir

Garoufis, A., Karidi, K., Hadjiliadis, N., Kasselouri, S., Kobe, J., Balzarini, J., ...

With the aim to improve and extend the antiviral activity of the antiherpic drug penciclovir, to a wider spectrum of viruses, we have synthesized and characterized new binary and ternary complexes of...

[18F]FDG and [18F]FLT uptake in human breast cancer cells in relation to the effects of chemotherapy: an in vitro study

Direcks, W G E, Berndsen, S C, Proost, N, Peters, G J, Balzarini, J, Spreeuwenberg, M D, ...

Increased 2′-deoxy-2′-[18F]fluoro-D-glucose (FDG) uptake is the most commonly used marker for positron emission tomography in oncology. However, a proliferation tracer such as...