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

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 µg·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 3 704 to 38 462 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.