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 μM, CC₅₀ of>1000 μM and selectivity index (SI) of>15,723. Zidovudine prodrug bearing ciprofloxacin and norfloxacin moiety showed 100% inhibition against Mycobacterium tuberculosis H₃₇Rv at 6.25 μg/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 t_1/2 ranging from 20 to 240 min.