title: Synthesis and in vitro antimycobacterial activity of compounds derived from (R)- and (S)-2-amino-1-butanol - The crucial role of the configuration.
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.
authors.affiliation: Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Bl. 9, Acad. G. Bonchev Str., Sofia 1113, Bulgaria. gmdob@orgchm.bas.bg
authors.forename: Georgi M
authors.initials: GM
authors.lastname: Dobrikov
authors.forename: Violeta
authors.initials: V
authors.lastname: Valcheva
authors.forename: Margarita
authors.initials: M
authors.lastname: Stoilova-Disheva
authors.forename: Georgi
authors.initials: G
authors.lastname: Momekov
authors.forename: Pavleta
authors.initials: P
authors.lastname: Tzvetkova
authors.forename: Angel
authors.initials: A
authors.lastname: Chimov
authors.forename: Vladimir
authors.initials: V
authors.lastname: Dimitrov
mesh_terms: D000605:Amino Alcohols / Q000737:chemistry / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development; D009904:Optical Rotation; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism
chemical_list: D000605:Amino Alcohols; D000995:Antitubercular Agents; C006506:2-amino-1-butanol