title: Synthesis of zidovudine derivatives with anti-HIV-1 and antibacterial activities.
abstract: Twelve novel zidovudine derivatives were prepared by modifying 5 '-hydroxyl group of sugar moiety (1-8) and 5-methyl group of thymidine nucleus (9-12) and characterized spectrally. The compounds were evaluated for anti-HIV-1, antitubercular and antibacterial activities. Compound (3-azido-tetrahydro-5- (3,4-dihydro-5-methyl-2,4-dioxopyrimidin-1(2H)-yl)furan-2-yl)methyl 7-(4-(2-phenylacetoyloxy)-3,5- dimethylpiperazin-1-yl)-5-(2-phenylacetoyloxyamino)-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate (5) was found to be the most potent anti-HIV-1 agent with EC(50) of 0.0012 microM against HIV-1(IIIB) and CC(50) of 34.05 microM against MT-4 with selectivity index of 28,375. Compound 5 inhibited Mycobacterium tuberculosis with MIC of 1.72 microM and inhibited four pathogenic bacteria with MIC of less than 1 microM.
authors.affiliation: Medicinal Chemistry & Antimycobacterial Research Laboratory, Pharmacy Group, Birla Institute of Technology & Science-Pilani, Hyderabad, Andhra Pradesh, India.
authors.forename: Palaniappan
authors.initials: P
authors.lastname: Senthilkumar
authors.forename: Jing
authors.initials: J
authors.lastname: Long
authors.forename: Raparla
authors.initials: R
authors.lastname: Swetha
authors.forename: Vaidyanathan
authors.initials: V
authors.lastname: Shruthi
authors.forename: Rui-Rui
authors.initials: RR
authors.lastname: Wang
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Preethi
authors.forename: Perumal
authors.initials: P
authors.lastname: Yogeeswari
authors.forename: Yong-Tang
authors.initials: YT
authors.lastname: Zheng
authors.forename: Dharmarajan
authors.initials: D
authors.lastname: Sriram
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D002460:Cell Line; D015195:Drug Design; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D013329:Structure-Activity Relationship; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents; D015215:Zidovudine