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 / 药学学报
Acta Pharmaceutica Sinica
; (12): 228-234, 2010.
Article
in En
| WPRIM
| ID: wpr-250658
Responsible library:
WPRO
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.
Full text:
1
Database:
WPRIM
Main subject:
Pharmacology
/
Pyrimidinones
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Virus Replication
/
Benzyl Compounds
/
Cell Line
/
Chemistry
/
HIV-1
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Reverse Transcriptase Inhibitors
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Anti-HIV Agents
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Drug Resistance, Viral
Limits:
Humans
Language:
En
Journal:
Acta Pharmaceutica Sinica
Year:
2010
Document type:
Article