Pyranocoumarins: A new class of anti-hyperglycemic and anti-dyslipidemic agents

• Published in: Bioorganic & medicinal chemistry letters Vol. 19; no. 22; pp. 6447 - 6451
• Main Authors: Kumar, Atul, Maurya, Ram Awatar, Sharma, Siddharth, Ahmad, Pervez, Singh, A.B., Bhatia, Gitika, Srivastava, Arvind K.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15-11-2009; Elsevier
• Subjects: Animals; Anti-dyslipidemic; Anti-hyperglycemic; Biological and medical sciences; Blood Glucose; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - drug therapy; Dyslipidemias - blood; Dyslipidemias - drug therapy; General and cellular metabolism. Vitamins; Hypoglycemic Agents - classification; Hypoglycemic Agents - therapeutic use; Lipid Metabolism - drug effects; Medical sciences; Mice; Mice, Inbred C57BL; Pharmacology. Drug treatments; PPAR gamma - metabolism; PTP 1B; Pyranocoumarins; Pyranocoumarins - metabolism; Pyranocoumarins - therapeutic use; Rats; Rats, Wistar; Structure-Activity Relationship; Pyranocoumarins; Anti-dyslipidemic; PTP 1B; Anti-hyperglycemic; Rat; Coumarine derivatives; Phosphoric monoester hydrolases; Esterases; Morpholine derivatives; Hypoglycemic agent; Piperidine derivatives; Chemical synthesis; Enzyme; Rodentia; Lactone; In vitro; Biological activity; In vivo; Vertebrata; Mammalia; Mouse; Animal; Gemfibrozil; Hydrolases; Antilipemic agent; Protein-tyrosine-phosphatase
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2009.09.031

A series of pyranocoumarin derivatives were synthesized and evaluated in vivo for their anti-hyperglycemic as well as anti-dyslipidemic activities. Compounds
7a,
7c,
8a,
8b,
8c,
8e and
8f have shown promising anti-hyperglycemic activities in sucrose loaded model (SLM) as well as sucrose challenged streptozotocin induced diabetic rat model (STZ). Compounds
8a and
8b were showing 38.0% and 42.0% blood glucose lowering activity in db/db mice model. In vitro anti-hyperglycemic activity evaluation exhibited that compounds
8a (IC
50
=
24.5
μM) and
8b (IC
50
=
36.2
μM) are potential PTP-1B inhibitors thereby revealing their possible mechanism of anti-diabetic action. Compounds
7a,
7b,
8a,
8b,
8d,
8e and
8f have shown significant anti-dyslipidemic activity in triton induced dyslipidemia in rats.