Quantitative Structure-Activity Relationship Studies on Some Viral Reverse Transcriptase Inhibitors Acting as Anti-Hiv-1 Agents

Abstract

The anti-HIV-1 and cytotoxic activities of some viral reverse transcriptase inhibitors, namely the analogues of [1-[2′,5′-bis-O-(tert-butyldimethylsilyl)-β-D-xylo-and-ribofuranosyl]]-3′-spiro-5″-[4″-amino-1″.2″-oxathiole 2″,2″-dioxide] (TSAO) pyrimidine and pyrimidine modified-nucleosides, are analysed in relation to their physicochemical and molecular properties. The antiviral activities of the compounds are found to be significantly correlated with hydrophobic and electronic properties of the molecules, but no physicochemical parameters were found to be correlated with the cytotoxic effects of the compounds. This difference is exploited to improve the selectivity of the compounds. It is observed that TSAO can provide potent anti-HIV-1 drugs with a disubstituted thymine ring, in which a substituent may be at the N₃-position. The disubstitution reduces the cytotoxicity, and substituents' hydrophobicity and electron donating character enhance the antiviral activity.

Key Words: :

• Quantitative structure-activity relationship
• HIV-1 reverse transcriptase inhibitors
• TSAO derivatives.