Synthesis, anti-HIV and antitubercular activities of lamivudine prodrugs.
The synthesis of a novel series of lamivudine prodrugs involving N4-substitution with isatin derivatives is described. The in-vitro antiretroviral activities indicated that compound 3b was found to be equipotent to lamivudine with EC50 of 0.0742+/-0.04 microM. Lamivudine prodrugs bearing fluoroquinoles antibacterial showed 92-100% inhibition against Mycobacterium tuberculosis strain H37Rv at 6.25 microg ml(-1). At pH 7.4, 37 degrees C, the hydrolytic t(1/2) ranged between 120 and 240 min.
Sriram
Dharmarajan
D
Medicinal Chemistry Research Laboratory, Pharmacy Group Birla Institute of Technology and Science, Pilani-333031, India. dsriram@bits-pilani.ac.in
Yogeeswari
Perumal
P
Gopal
Gayatri
G
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D045744:Cell Line, Tumor; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D019259:Lamivudine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D000995:Antitubercular Agents; D011355:Prodrugs; D019259:Lamivudine