title: Design, synthesis and antimycobacterial activities of 1-methyl-2-alkenyl-4(1H)-quinolones.
abstract: A series of 23 new 1-methyl-2-alkenyl-4(1H)quinolones have been synthesized and evaluated in vitro for their antimycobacterial activities against fast growing species of mycobacteria, such as Mycobacterium fortuitum, M. smegmatis and M. phlei. The compounds displayed good to excellent inhibition of the growth of the mycobacterial test strains with improved antimycobacterial activity compared to the hit compound, evocarpine. The most active compounds, which possessed chain length of 11-13 carbons at position-2 displayed potent inhibitory effects with an MIC value of 1.0mg/L. In a human diploid embryonic lung cell line, MRC-5 cytotoxicity assay, the alkaloids showed weak to moderate cytotoxic activity. Biological evaluation of these evocarpine analogues on the less pathogenic fast growing strains of mycobacteria showed an interesting antimycobacterial profile and provided significant insight into the structure-activity relationships.
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Universitätsplatz 4/1, 8010 Graz, Austria.
authors.forename: Abraham A
authors.initials: AA
authors.lastname: Wube
authors.forename: Antje
authors.initials: A
authors.lastname: Hüfner
authors.forename: Christina
authors.initials: C
authors.lastname: Thomaschitz
authors.forename: Martina
authors.initials: M
authors.lastname: Blunder
authors.forename: Manfred
authors.initials: M
authors.lastname: Kollroser
authors.forename: Rudolf
authors.initials: R
authors.lastname: Bauer
authors.forename: Franz
authors.initials: F
authors.lastname: Bucar
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000995:Antitubercular Agents; D015363:Quinolones