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Design, synthesis and antimycobacterial activities of 1-methyl-2-alkenyl-4(1H)-quinolones |
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| Authors: | Wube Abraham A Hüfner Antje Thomaschitz Christina Blunder Martina Kollroser Manfred Bauer Rudolf Bucar Franz |
| Affiliation: | a Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Universitätsplatz 4/1, 8010 Graz, Austria b Institute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, University of Graz, Universitätsplatz 1, 8010 Graz, Austria c Institute of Forensic Medicine, Medical University of Graz, Universitätsplatz 4/2, 8010 Graz, Austria |
| 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 1.0 mg/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. |
| Keywords: | 1-Methyl-2-alkenyl-4(1H)-quinolone Antimycobacterial Tuberculosis SAR |
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