Synthesis of zidovudine prodrugs with broad-spectrum chemotherapeutic properties for the effective treatment of HIV/AIDS.

A series of prodrugs of zidovudine has been synthesized in an effort to enhance spectrum of chemotherapeutic properties for the effective treatment of HIV/AIDS. The 5'-OH function of zidovudine was esterified with ciprofloxacin, norfloxacin, isoniazide, pyrazinamide acetic acid. The anti-HIV-1 activity of the esters was determined in CEM cell-line and zidovudine ester bearing pyrazinamide acetic acid was found to be the most potent compound with EC50 of<0.0636 microM, CC50 of>1000 microM and selectivity index (SI) of>15,723. Zidovudine prodrug bearing ciprofloxacin and norfloxacin moiety showed 100% inhibition against Mycobacterium tuberculosis H37Rv at 6.25 microg/ml. The prodrugs were also found to exhibit antibacterial activity against 24 pathogenic bacteria. In vitro hydrolysis of the various esters in human plasma indicated that these agents were relatively stable toward plasma esterase with t1/2 ranging from 20 to 240 min.

Newer aminopyrimidinimino isatin analogues as non-nucleoside HIV-1 reverse transcriptase inhibitors for HIV and other opportunistic infections of AIDS: design, synthesis and biological evaluation.

Human immuno deficiency virus (HIV) weakens the immune system so that many opportunistic infections (OIs) like tuberculosis, hepatitis, bacterial infections etc can develop. In this paper, we designed aminopyrimidinimino isatin lead compound as a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) with broad-spectrum chemotherapeutic properties for the effective treatment of AIDS and AIDS-related OIs. Compound 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-[[N4-[3'-(4'-amino-5'-trimethoxybenzyl pyrimidin-2'-yl)imino-1'-(5-methylisatinyl)]methyl]-N1-piperazinyl]-3-quinoline carboxylic acid (10) emerged as the most potent broad-spectrum chemotherapeutic agent active against HIV, HCV, Mycobacterium tuberculosis and various pathogenic bacteria.