Heterocycles [h]-fused onto 4-oxoquinoline-3-carboxylic acid, part VIII [1]. Convenient synthesis and antimicrobial properties of substituted hexahydro[1,4]diazepino[2,3-h]quinoline-9-carboxylic acid and its tetrahydroquino[7,8-b]benzodiazepine analog.
[1,4]Diazepino[2,3-h]quinolone carboxylic acid 3 and its benzo-homolog tetrahydroquino[7,8-b]benzodiazepine-3-carboxylic acid 5 were prepared via PPAcatalyzed thermal lactamization of the respective 8-amino-7-substituted-1,4-dihydroquinoline-3-carboxylic acid derivatives 8, 10. The latter compounds were obtained by reduction of their 8-nitro-7-substituted-1,4-dihydroquinoline-3-carboxylic acid precursors 7, 9 which, in turn, were prepared by reaction of 7-chloro-1-cyclopropyl-6-fluoro-8-nitro-1,4-dihydroquinoline-3-carboxylic acid (6) with each of beta-alanine and anthranilic acid. All intermediates and target compounds were characterized using elemental analysis, NMR, IR and MS spectral data. The prepared targets and the intermediates have shown interesting antibacterial activity mainly against Gram positive strains. In particular, compound 8 showed good activity against S. aureus (MIC = 0.39 microg/mL) and B. subtilis (MIC = 0.78 microg/mL). Compounds 5a and 9 have also displayed good antifungal activity against C. albicans (MIC = 1.56 microg/mL and 0.78 microg/mL, respectively). None of the compounds tested showed any anticancer activity against solid breast cancer cell line MCF-7 cells or a human breast adenocarcinoma cell line.
Al-Hiari
Yusuf M
YM
Department of Pharmaceutical Sciences, Faculty of Pharmacy, The University of Jordan, Amman, Jordan. hiary@ju.edu.jo
Abu-Dahab
Rana
R
El-Abadelah
Mustafa M
MM
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001381:Azepines / Q000737:chemistry / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects; D001569:Benzodiazepines / Q000737:chemistry / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004847:Epithelial Cells / Q000187:drug effects; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D001381:Azepines; D002264:Carboxylic Acids; D006571:Heterocyclic Compounds; D011804:Quinolines; D015363:Quinolones; C533968:diazepino(2,3-h)quinoline; C533971:quino(7,8-b)benzodiazepine; D001569:Benzodiazepines