title: Identification of benzofuro[2,3-b]quinoline derivatives as a new class of antituberculosis agents.
abstract: A series of 11-alkoxylated and 11-aminated benzofuro[2,3-b]quinoline derivatives were designed, synthesized, and evaluated for their anti-TB and cytotoxic activities. The known 11-chlorobenzofuro[2,3-b]quinoline (3) was synthesized in a single step from anthranilic acid and 2-coumaranone in phosphorus oxychloride in 51% yield for the first time. Treatment of 3 with alcohols and amines gave 11-alkoxylated and 11-aminated benzofuro[2,3-b]quinoline derivatives respectively, which were evaluated for their anti-TB and cytotoxic activities. Our results indicated that 11-arylaminated derivatives were more active than their respective 11-aryloxylated isosteric isomers against Mycobacterium tuberculosis. Among the tested compounds, 11-methoxybenzofuro[2,3-b]quinoline (4), 11-methylamino- benzofuro[2,3-b]quinoline (9), and 11-dimethylaminobenzofuro[2,3-b]quinoline (14) exhibited significant activities against the growth of M. tuberculosis (MIC values of <0.20 microg/mL) and low cytotoxicities against VERO cell with IC(50) values of 11.77, 5.55, and >30.00 microg/mL respectively. The selectivity index (SI=IC(50)/MIC) for 4, 9, and 14 was greater than 58.85, 27.75, and 150 respectively.
authors.affiliation: Department of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung City 807, Taiwan.
authors.forename: Chiao-Li
authors.initials: CL
authors.lastname: Yang
authors.forename: Chih-Hua
authors.initials: CH
authors.lastname: Tseng
authors.forename: Yeh-Long
authors.initials: YL
authors.lastname: Chen
authors.forename: Chih-Ming
authors.initials: CM
authors.lastname: Lu
authors.forename: Chai-Lin
authors.initials: CL
authors.lastname: Kao
authors.forename: Ming-Hsien
authors.initials: MH
authors.lastname: Wu
authors.forename: Cherng-Chyi
authors.initials: CC
authors.lastname: Tzeng
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D001572:Benzofurans / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000995:Antitubercular Agents; D001572:Benzofurans; D011804:Quinolines