title: Synthesis, antibacterial, antifungal and anti-HIV activities of norfloxacin mannich bases.
abstract: Mannich bases of norfloxacin were synthesized by reacting them with formaldehyde and several isatin derivatives. Their chemical structures have been confirmed by means of their IR, 1H-NMR data and by elemental analysis. Investigation of in vitro antimicrobial activity of compounds was done by the agar dilution method against 28 pathogenic bacteria, eight pathogenic fungi and anti-HIV activity against replication of HIV-1 (III B) in MT-4 cells. The in vivo antibacterial efficacy of selected derivatives was determined using a mouse infection model. All the synthesized compounds are more active than norfloxacin against the 13 bacteria tested. The compounds are also more active than the standard drug clotrimazole against Histoplasma capsulatum. Two compounds S-8 and S-9 have shown inhibition against HIV-1 (III B) with EC(50) values of 11.3 and 13.9 microgram/mL, respectively. In the mouse protection test, two compounds S-4 (ED(50): 1.25 mg/kg) and S-9 (ED(50): 1.62 mg/kg) are more active than norfloxacin (ED(50): 6mg/kg). Among the compounds tested, 1-ethyl-6-fluoro-1, 4-dihydro-4-oxo-7[[N(4)-[5'-bromo-3'-(4'-amino-5'-trimethoxybenzylpyr imidin-2'-yl]-imino-1'-isatinyl]methyl]N(1)-piperazinyl]-3-q uinoline carboxylicacid (S-9) showed promising activity in all the three tests.
authors.affiliation: Department of Pharmaceutics, Institute of Technology, Banaras Hindu University, Varanasi, India. snpande@banaras.ernet.in
authors.forename: S N
authors.initials: SN
authors.lastname: Pandeya
authors.forename: D
authors.initials: D
authors.lastname: Sriram
authors.forename: G
authors.initials: G
authors.lastname: Nath
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D001424:Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D005658:Fungi / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects; D007928:Lethal Dose 50; D008297:Male; D008352:Mannich Bases / Q000138:chemical synthesis / Q000494:pharmacology; D051379:Mice; D008826:Microbial Sensitivity Tests; D009643:Norfloxacin / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000633:toxicity; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D000890:Anti-Infective Agents; D000935:Antifungal Agents; D008352:Mannich Bases; D009643:Norfloxacin