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

• DOI: 10.1016/j.ejmech.2011.11.035
• Publication Date: 2011-12-12T14:47:43Z
• Authors: Georgi M. Dobrikov; Violeta Valcheva; Margarita Stoilov...; Georgi Momekov; Pavleta Tzvetkova; Angel Chimov; Vladimir Dimitrov
• Keywords: Antimycobacterial

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.