The (S)- and (R)-enantiomers of 9-(2-phosphonylmethoxypropyl) derivatives of adenine (PMPA) and 2,6-diaminopurine (PMPDAP) were evaluated for their inhibitory effect on HIV replication in several human cell systems, including natural peripheral blood lymphocytes (PBL) and freshly isolated monocyte/macrophages (M/M). The (R)-enantiomers of PMPDAP and PMPA were ~10- to 100-fold more effective against HIV than their (S)-enantiomeric counterparts. The antiviral efficacy of (R)-PMPA was comparable to that of the prototype acyclic nucleoside phosphonate 9-(2-phosphonylmethoxyethyl)adenine (PMEA). The most potent and selective HIV inhibitor was (R)-PMPDAP. Its 50% effective concentration ranged from 0.01 μM for HIV-1/Ba-L in M/M to 1-2.8 μM for HIV-1/III(B), and HIV-1/HE in C8166, GEM, Molt/4, MT-4 and PBL cells. Both (R)-PMPA and (R)-PMPDAP were not toxic to the host cells at 300 μM.

Balzarini, J., Aquaro, S., Perno, C.f., Witvrouw, M., Holy, A., De Clercq, E. (1996). Activity of the (R)-Enantiomers of 9-(2-phosphonylmethoxypropyl)-adenine and 9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine against human immunodeficiency virus in different human cell systems. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 219(2), 337-341 [10.1006/bbrc.1996.0234].

Activity of the (R)-Enantiomers of 9-(2-phosphonylmethoxypropyl)-adenine and 9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine against human immunodeficiency virus in different human cell systems

AQUARO, STEFANO;PERNO, CARLO FEDERICO;
1996-01-01

Abstract

The (S)- and (R)-enantiomers of 9-(2-phosphonylmethoxypropyl) derivatives of adenine (PMPA) and 2,6-diaminopurine (PMPDAP) were evaluated for their inhibitory effect on HIV replication in several human cell systems, including natural peripheral blood lymphocytes (PBL) and freshly isolated monocyte/macrophages (M/M). The (R)-enantiomers of PMPDAP and PMPA were ~10- to 100-fold more effective against HIV than their (S)-enantiomeric counterparts. The antiviral efficacy of (R)-PMPA was comparable to that of the prototype acyclic nucleoside phosphonate 9-(2-phosphonylmethoxyethyl)adenine (PMEA). The most potent and selective HIV inhibitor was (R)-PMPDAP. Its 50% effective concentration ranged from 0.01 μM for HIV-1/Ba-L in M/M to 1-2.8 μM for HIV-1/III(B), and HIV-1/HE in C8166, GEM, Molt/4, MT-4 and PBL cells. Both (R)-PMPA and (R)-PMPDAP were not toxic to the host cells at 300 μM.
1996
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA
English
Con Impact Factor ISI
9 (2 phosphonylmethoxypropyl) 2,6 diaminopurine; acyclic nucleoside; adefovir; adenine derivative; purine derivative; tenofovir; unclassified drug; antiviral activity; article; concentration response; controlled study; drug potency; human; human cell; Human immunodeficiency virus; Human immunodeficiency virus 1; macrophage; monocyte; nonhuman; peripheral lymphocyte; priority journal; virus replication; Adenine; Antiviral Agents; Cell Line; Dose-Response Relationship, Drug; HIV-1; Humans; Organophosphorus Compounds; Phosphonic Acids; Soman; Stereoisomerism; Structure-Activity Relationship; Virus Replication
Balzarini, J., Aquaro, S., Perno, C.f., Witvrouw, M., Holy, A., De Clercq, E. (1996). Activity of the (R)-Enantiomers of 9-(2-phosphonylmethoxypropyl)-adenine and 9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine against human immunodeficiency virus in different human cell systems. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 219(2), 337-341 [10.1006/bbrc.1996.0234].
Balzarini, J; Aquaro, S; Perno, Cf; Witvrouw, M; Holy, A; De Clercq, E
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/51563
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