Synthesis of 1,3-thiazine derivatives and their evaluation as potential antimycobacterial agents.
A series of eight 5,6-dihydro-4H-1,3-thiazine derivatives was synthesized by the BF3 x Et2O-catalyzed reaction of selected alpha,beta-unsaturated ketones with thiobenzamide at room temperature. The antimycobacterial activities of these compounds were determined against Mycobacterium tuberculosis H37Rv (ATCC 27294) using the Alamar blue susceptibility assay. Three compounds, 5-hydroxy-3-phenyl-4-aza-2-thiabicyclo[3.3.1]none-3-ene 3a, 4-hydroxy-4-methyl-6-pentyl-2-phenyl-5,6-dihydro-4H-1,3-thiazine 3b, and 4-ethyl-4-hydroxy-2-phenyl-5,6-dihydro-4H-1,3-thiazine 3c exhibited inhibitory activities of 97, 77 and 76%, respectively, at a concentration of 6.25 microg/ml. The actual MIC99 for the most active of these compounds, 3a, was also determined to be >6.25 microg/ml. These results, and especially those for 3a, suggest that 1,3-thiazines are potential lead compounds in the search for new antitubercular agents.
Koketsu
Mamoru
M
Department of Chemistry, Faculty of Engineering, Gifu University, Yanagido 1-1, 501-1193, Japan. koketsu@cc.gifu-u.ac.jp
Tanaka
Kohsuke
K
Takenaka
Yuichi
Y
Kwong
Cecil D
CD
Ishihara
Hideharu
H
D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000254:growth & development; D013843:Thiazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000995:Antitubercular Agents; D013843:Thiazines