Beta-lactam congeners of orlistat as inhibitors of fatty acid synthase.
Beta-lactam derivatives of orlistat were prepared and their inhibitory activities toward the thioesterase domain of fatty acid synthase (FAS-TE) were evaluated using a recombinant form of the enzyme. While in general these derivatives showed lower potency compared to beta-lactones, a reasonably potent, lead compound (-)-9 (IC(50)=8.6microM) was discovered that suggests that this class of compounds should be evaluated further.
Zhang
Wei
W
Department of Chemistry, Texas A&M University, College Station, TX 77842-3012, USA.
Richardson
Robyn D
RD
Chamni
Supakarn
S
Smith
Jeffrey W
JW
Romo
Daniel
D
D019440:Anti-Obesity Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors*; D006801:Humans; D020128:Inhibitory Concentration 50; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D008956:Models, Chemical; D000077403:Orlistat; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D047090:beta-Lactams / Q000138:chemical synthesis / Q000494:pharmacology*
D019440:Anti-Obesity Agents; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D007783:Lactones; D047090:beta-Lactams; D000077403:Orlistat; D064429:Fatty Acid Synthases