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

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 H37Rv showing no activity even at 20–32 fold higher concentrations.

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► We synthesized 47 diverse derivatives of (R)-2-amino-1-butanol, structure analogues of EMB.
► 5 compounds possess in vitro antimycobacterial activity – 5.7–11.1 fold more active than EMB.
► We synthesized the S-enantiomers of above mentioned 5 compounds and they showed no activity.