1. The anti-HIV activity of three 2-alkylsulfanyl-6-benzyl-3, 4-dihydropyrimidin-4 (3H)-one derivatives acting as non-nucleoside reverse transcriptase inhibitor in vitro.
- Author
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Long J, Zhang DH, Zhang GH, Rao ZK, Wang YH, Tam SC, He YP, and Zheng YT
- Subjects
- Anti-HIV Agents chemical synthesis, Anti-HIV Agents chemistry, Benzyl Compounds chemical synthesis, Benzyl Compounds chemistry, Cell Line, Drug Resistance, Viral, HIV Reverse Transcriptase antagonists & inhibitors, HIV Reverse Transcriptase metabolism, Humans, Pyrimidinones chemical synthesis, Pyrimidinones chemistry, Reverse Transcriptase Inhibitors chemical synthesis, Reverse Transcriptase Inhibitors chemistry, Virus Replication drug effects, Anti-HIV Agents pharmacology, Benzyl Compounds pharmacology, HIV-1 drug effects, Pyrimidinones pharmacology, Reverse Transcriptase Inhibitors pharmacology
- Abstract
It was recently shown that several new synthetic 2-alkylsulfanyl-6-benzyl-3, 4-dihydropyrimidin-4(3H)-one (S-DABO) derivatives demonstrated anti-HIV-1 activity. Three of the derivatives namely RZK-4, RZK-5 and RZK-6 were used in this study to explore their inhibitory effects on a variety of HIV strains. These compounds at a concentration of 200 microg mL(-1) almost completely inhibited the activity of recombinant HIV-1 reverse transcriptase. All of the three compounds reduced replication of HIV-1 laboratory-derived strains, low-passage clinical isolated strain, and the drug resistant strain. In particular RZK-6 showed potent activity against the HIV-1 drug resistant strain. In general, the antiviral activities are similar in magnitude to nevirapine (NVP), which is a non-nucleoside reverse transcriptase inhibitor approved by FDA. The therapeutic indexes of these compounds were remarkable, ranging from 3704 to 38462 indicating extremely low cytotoxicity. These results suggest that the three S-DABO derivatives in this study have good potential for further development in anti-HIV-1 therapy. It may be particularly useful to target at the non-nucleoside reverse transcriptase inhibitors resistant HIV-1 strain.
- Published
- 2010