Synthesis, anti-HIV and antitubercular activities of nelfinavir diester derivatives.
Nelfinavir diesters were prepared by reacting nelfinavir with two molar amount of an appropriate substituted aromatic/aliphatic acid in the presence of dicylohexyl carbodiimide as the carboxyl group activator and 4-dimethylamino pyridine as catalyst. The synthesized compounds were evaluated for their inhibitory effects on the replication of HIV-1 (IIIB) in MT-4 cells by MTT assay method and antimycobacterial activity against Mycobacterium tuberculosis H37Rv by agar dilution method. Compound 3f emerged as the most potent anti-HIV agent with EC(50) of 0.043 microM and CC(50) more than >10 microM and was more potent than parent nelfinavir (EC(50) of 0.060 microM) and also showed antimycobacterial activity (MIC 8.49 microM).
Sriram
Dharmarajan
D
Medicinal Chemistry Research Laboratory, Pharmacy Group, Birla Institute of Technology & Science, Pilani, Rajasthan, India. dsiram@bits-pilani.ac.in
Yogeeswari
Perumal
P
Dinakaran
Murugesan
M
Sowmya
Mannila
M
D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002460:Cell Line; D004952:Esters / Q000138:chemical synthesis / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D019888:Nelfinavir / Q000737:chemistry / Q000494:pharmacology*
D019380:Anti-HIV Agents; D000995:Antitubercular Agents; D004952:Esters; D019888:Nelfinavir