European Journal of Medicinal Chemistry 2012-02-01

Synthesis and in vitro antimycobacterial activity of compounds derived from (R)- and (S)-2-amino-1-butanol - The crucial role of the configuration.

Georgi M Dobrikov, Violeta Valcheva, Margarita Stoilova-Disheva, Georgi Momekov, Pavleta Tzvetkova, Angel Chimov, Vladimir Dimitrov

Index: Eur. J. Med. Chem. 48 , 45-56, (2012)

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Abstract

The synthesis of 47 structurally diverse compounds incorporating the (R)-2-amino-1-butanol motif has been realized. Ten of these compounds were found to exhibit in vitro specific activity against Mycobacterium tuberculosis H37Rv in a MIC range of 0.65 μM-14.03 μM. Five of the most active compounds 11, 22, 23, 31 and 42 (5.7-11.1 fold more active than ethambutol) can be outlined with very low cytotoxicity towards human embryonal kidney non-tumour cells (SI ranging from 91.2 to 375.4). For the purpose of comparison the (S)-enantiomers of these most active compounds have been synthesized and evaluated towards M. tuberculosis H(37)Rv showing no activity even at 20-32 fold higher concentrations.Copyright © 2011 Elsevier Masson SAS. All rights reserved.