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:
Jing LONG
1
;
De-hua ZHANG
;
Gao-hong ZHANG
;
Zhi-kun RAO
;
Yun-hua WANG
;
Siu-cheung TAM
;
Yan-ping HE
;
Yong-tang ZHENG
Author Information
1. Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
- Publication Type:Journal Article
- MeSH:
Anti-HIV Agents;
chemical synthesis;
chemistry;
pharmacology;
Benzyl Compounds;
chemical synthesis;
chemistry;
pharmacology;
Cell Line;
Drug Resistance, Viral;
HIV Reverse Transcriptase;
antagonists & inhibitors;
metabolism;
HIV-1;
drug effects;
Humans;
Pyrimidinones;
chemical synthesis;
chemistry;
pharmacology;
Reverse Transcriptase Inhibitors;
chemical synthesis;
chemistry;
pharmacology;
Virus Replication;
drug effects
- From:
Acta Pharmaceutica Sinica
2010;45(2):228-234
- CountryChina
- Language:English
-
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.
