Synthesis and biological activity of enantiomeric pairs of 5-[(E)-cycloalk-2-enylidenemethyl]thiolactomycin congeners.
The title congeners were synthesized by employing our efficient synthetic route previously explored for preparing enantiomeric pairs of thiolactomycin and its 3-demethyl derivative. While all the synthesized congeners lacked in vitro antibacterial activity, some of the congeners bearing an (E)-cyclohept-2-enylidenemethyl or an (E)-cyclooct-2-enylidenemethyl group were found to exhibit more potent type I FAS inhibitory activity than (S)-3-demethylthiolactomycin having an unnatural configuration.
Ohata
Kohei
K
Kyorin Pharmaceutical Co., Ltd, Discovery Research Laboratories, 2399-1 Nogi, Nogi-Machi, Shimotsuga, Tochigi 329-0114, Japan. kouhei.oohata@mb.kyorin-pharm.co.jp
Terashima
Shiro
S
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry; D000890:Anti-Infective Agents / Q000737:chemistry; D002460:Cell Line; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D008956:Models, Chemical; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D013876:Thiophenes; C035068:thiolactomycin; D064429:Fatty Acid Synthases