Quantitative structure-activity relationship studies on some viral reverse transcriptase inhibitors acting as anti-HIV-1 agents.
The anti-HIV-1 and cytotoxic activities of some viral reverse transcriptase inhibitors, namely the analogues of [1-[2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-xylo- and -ribofuranosyl]]-3'-spiro-5" -[4"-amino-1",2"-oxathiole 2",2"-dioxide] (TSAO) pyrimidine and pyrimidine modified-nucleotides, 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.
Garg
R
R
Department of Chemistry, Birla Institute of Technology & Science, Pilani, India.
Gupta
S P
SP
D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008956:Models, Chemical; D015394:Molecular Structure; D011743:Pyrimidines / Q000494:pharmacology; D012044:Regression Analysis; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013141:Spiro Compounds / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013936:Thymidine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D014529:Uridine / Q000031:analogs & derivatives
D019380:Anti-HIV Agents; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; D013141:Spiro Compounds; D054303:HIV Reverse Transcriptase; D013936:Thymidine; C075132:TSAO-T; D014529:Uridine