Preparation and in vitro evaluation of benzylsulfanyl benzoxazole derivatives as potential antituberculosis agents.
A set of 2-benzylsulfanyl derivatives of benzoxazole was synthesized and evaluated for their in vitro antimycobacterial activity against Mycobacterium tuberculosis, non-tuberculous mycobacteria and multidrug-resistant M. tuberculosis. The activities were expressed as the minimum inhibitory concentration (MIC) in mmol/L. The substances showed similar activity against all tested strains. The lead compounds in the set, dinitro derivatives exhibited significant activity against both sensitive and resistant strains of M. tuberculosis and also against non-tuberculous mycobacteria. To facilitate drug design of benzoxazole as potential antituberculosis agent, we have explored the quantitative structure-activity relationship (QSAR). We demonstrated that lower lipophilicity has significant contribution to activity. Dinitrobenzylsulfanyl derivative of benzoxazole represents the promising small-molecule synthetic antimycobacterials.
Klimesová
Vera
V
Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, Heyrovského 1203, Hradec, Králové, 500 05, Czech Republic.
Kocí
Jan
J
Waisser
Karel
K
Kaustová
Jarmila
J
Möllmann
Ute
U
D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001583:Benzoxazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D021281:Quantitative Structure-Activity Relationship
D000995:Antitubercular Agents; D001583:Benzoxazoles