Mono- and disalicylic acid derivatives: PTP1B inhibitors as potential anti-obesity drugs.
A series of compounds containing one or two salicylic acid moieties were synthesized, and their efficacy to inhibit the phosphohydrolase activity of PTP1B examined. Some of the methylenedisalicylic acid derivatives were potent inhibitors of PTP1B. Of those derivatives, 3c exhibited about a 14-fold selectivity against TC-PTP, and this compound was tested in a mouse model for its efficacy to prevent diet-induced obesity. It effectively suppressed the increases in body weight and adipose mass, without any noticeable toxic effect. The compound also prevented increases in the plasma triglyceride, cholesterol, and nonesterified fatty acid concentrations; thus, expanding its therapeutic potential to other related metabolic diseases, such as hyperlipidemia and hypercholesterolemia.
Shrestha
Suja
S
Department of Chemistry and Institute of Molecular Cell Biology, College of Natural Sciences, Inha University, Incheon 402-751, Republic of Korea.
Bhattarai
Bharat Raj
BR
Lee
Keun-Hyeung
KH
Cho
Hyeongjin
H
D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D009765:Obesity / Q000517:prevention & control; D009929:Organ Size / Q000187:drug effects; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012459:Salicylates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D019440:Anti-Obesity Agents; D004791:Enzyme Inhibitors; D012459:Salicylates; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516609:Ptpn1 protein, mouse