Pyranocoumarins: a new class of anti-hyperglycemic and anti-dyslipidemic agents.
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 microM) and 8b (IC(50)=36.2 microM) 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.
Kumar
Atul
A
Medicinal and Process Chemistry Division, Central Drug Research Institute, Council of Scientific & Industrial Research, Lucknow 226001, India. dratulsax@gmail.com
Maurya
Ram Awatar
RA
Sharma
Siddharth
S
Ahmad
Pervez
P
Singh
A B
AB
Bhatia
Gitika
G
Srivastava
Arvind K
AK
D000818:Animals; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000145:classification / Q000627:therapeutic use; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000378:metabolism; D039681:Pyranocoumarins / Q000378:metabolism / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D039681:Pyranocoumarins