Jain Mohit M, Kumari Nirmala, Rai Geeta
Neiss Wellness India Limited, Mumbai 400064, India.
Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi 221005, India.
Int J Comput Biol Drug Des. 2015;8(1):54-61. doi: 10.1504/IJCBDD.2015.068787. Epub 2015 Apr 13.
Calcitonin gene-related peptide (CGRP) is involved in triggering migraine. Many strategies for antimigraine drug designing have been employed using various CGRP antagonist/ligands but most of them have failed due to their inability to reach target CGRP receptor as they get metabolised before conferring their pharmacological action and they are also toxic to the liver. In the present study, we evaluated the binding of our active ligands present in real veggies with the CGRP receptor crystal structure and compared their binding energy and affinity with other reference anti-migraine drugs/ligands present in the market. A high-throughput screening comprising of molecular docking, Absorption, Distribution, Metabolism, Excretion and Toxicity predictions, logP values and % of human oral absorption value led to the identification of two potential compounds present in live green real veggies which could be considered for anti-migraine activity with better binding affinities than the reference drugs used and with liver-protective properties.
降钙素基因相关肽（CGRP）参与偏头痛的触发。人们采用了多种策略，利用各种CGRP拮抗剂/配体来设计抗偏头痛药物，但其中大多数都失败了，因为它们在发挥药理作用之前就被代谢，无法到达目标CGRP受体，而且它们对肝脏也有毒性。在本研究中，我们评估了真实蔬菜中存在的活性配体与CGRP受体晶体结构的结合情况，并将它们的结合能和亲和力与市场上其他参考抗偏头痛药物/配体进行了比较。通过包括分子对接、吸收、分布、代谢、排泄和毒性预测、logP值以及人体口服吸收值百分比在内的高通量筛选，我们鉴定出了两种存在于新鲜绿色真实蔬菜中的潜在化合物，它们具有比所用参考药物更好的结合亲和力和肝脏保护特性，可考虑用于抗偏头痛活性。
