Bioorganic & Medicinal Chemistry Letters ( IF 2.5 ) Pub Date : 2019-10-28 , DOI: 10.1016/j.bmcl.2019.126759 Sarita Singh 1 , Karishma Agarwal 1 , Hina Iqbal 2 , Pankaj Yadav 2 , Deepika Yadav 3 , Debabrata Chanda 2 , Sudeep Tandon 4 , Feroz Khan 3 , Anil Kumar Gupta 5 , Atul Gupta 1
A series of substituted 8,8-dimethyl-8H-pyrano[2,3-f]chromen-2-ones (chromeno-coumarin hybrids) was synthesized from scopoletin (11) as vasorelaxing agents. The synthesized compounds 21a-f, 22, 23a-e and scopoletin (11) were evaluated for vasorelaxation in endothelium intact rat main mesenteric artery (MMA). Compounds 11, 21a, 21c-f and 22 showed significant vasorelaxation in precontracted MMA within the range of EC50 value 1.58-5.02 µM. These derivatives presented 29.40-70.89 fold increased sensitivity for experimental tissue compared to scopoletin (11), the parent molecule. Among others, 22 was found to be the most active compound which had EC50 1.58µM with 70.89 fold increased sensitivity. The mechanistic evaluation of 22 showed that it exerted vasorelaxation through Ca2+-activated K+ (BKca) channel and the effect was endothelium-independent.
中文翻译:
合成和评估取代的8,8-二甲基-8H-吡喃并[2,3-f] chromen-2-one衍生物作为血管舒张剂。
从草素(11)作为血管舒张剂合成了一系列取代的8,8-二甲基-8 H-吡喃并[2,3- f ] chromen -2-ones(chromeno-coumarin hybrids)。评估了合成的化合物21a-f, 22、23a -e和scopoletin(11)在内皮完整的大鼠主肠系膜动脉(MMA)中的血管舒张作用。化合物11,21A,21C - ˚F和22 EC的范围内预收缩MMA表明显著血管舒张50值1.58-5.02μM。与东pole碱相比,这些衍生物对实验组织的敏感性提高了29.40-70.89倍(11),母体分子。其中,发现22种化合物的活性最高,其EC 50为1.58µM,灵敏度提高70.89倍。对22种化合物的机械评价表明,它通过Ca 2+激活的K +(BKca)通道发挥血管舒张作用,且其作用与内皮无关。