Medicinal and Process Chemistry Division, Central Drug Research Institute, Council of Scientific & Industrial Research, Lucknow 226001, India.
Bioorg Med Chem Lett. 2009 Nov 15;19(22):6447-51. doi: 10.1016/j.bmcl.2009.09.031. Epub 2009 Sep 12.
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.
合成了一系列吡喃香豆素衍生物，并对其体内抗高血糖和抗血脂异常活性进行了评价。化合物 7a、7c、8a、8b、8c、8e 和 8f 在蔗糖负荷模型（SLM）以及蔗糖挑战链脲佐菌素诱导的糖尿病大鼠模型（STZ）中表现出有希望的抗高血糖活性。化合物 8a 和 8b 在 db/db 小鼠模型中显示出 38.0%和 42.0%的降血糖活性。体外抗高血糖活性评价表明，化合物 8a（IC50=24.5μM）和 8b（IC50=36.2μM）是潜在的 PTP-1B 抑制剂，从而揭示了它们可能的抗糖尿病作用机制。化合物 7a、7b、8a、8b、8d、8e 和 8f 在大鼠的 Triton 诱导的血脂异常中表现出显著的抗血脂异常活性。
