Planta Med 2010; 76 - P434
DOI: 10.1055/s-0030-1264732

In vitro antimycobacterial activity of synthetic 1-methyl-2-alkenyl-4(1H)-quinolones against Mycobacterium smegmatis

A Wube 1, A Hüfner 2, C Hochfellner 1, C Thomaschitz 1, R Bauer 1, F Bucar 1
  • 1Karl-Franzens University, Institute of Pharmaceutical sciences, Department of Pharmacognosy, Pharmacognosy, Universitätsplatz 4/1, 8010 Graz, Austria
  • 2Karl-Franzens University, Institute of Pharmaceutical sciences, Department of Pharmaceutical Chemistry, Pharmaceutical Chemistry, Universitätzplatz 1/1, 8010 Graz, Austria

Since long quinolones are widely used in the treatment of many types of infectious diseases caused by bacteria, including tuberculosis. Previously we have disclosed the antimycobacterial properties of natural 1-methyl-2-alkyl-4-(1H)-quinolone alkaloids isolated from Evodia rutaecarpa (Hook f. and Thomson. (Rutaceae) [1]. In our attempt to optimize the antimycobacterial potential of these new class of alkaloids, we have synthesized a wide range of derivatives having aliphatic side chain at position-2 with varying chain length and double bond position.


Tested against M. smegmatis ATCC 14468 using the microbroth dilution assay [2], the synthetic derivatives containing C10-C17 aliphatic side chain showed more potency (MIC's values 0.5–16µg/mL) compared to the natural products and even the standard drugs ethambutol and isoniazid. The structure-activity relationship study revealed that the size of the aliphatic side chain is essential for the observed antimycobacterial effects.

Acknowledgements: This work is financially supported by Austrian Science Fund (FWF) Project No. P21152-B18.

References: 1. Adams, M. et al (2004) Planta Med. 70; 904–908.

2. Wube, AA. Et al. (2005) Phytochemistry 66; 2309–2315.