Title:Quinoline Derivatives: Candidate Drugs for a Class B G-Protein Coupled Receptor, the Calcitonin Gene-Related Peptide Receptor, a Cause of Migraines
Volume: 13
Issue: 7
Author(s): Hira Iftikhar, Iqra Ahmad, Siew H. Gan, Munvar M. Shaik, Naveed Iftikhar, Muhammad S. Nawaz, Nigel H. Greig and Mohammad A. Kamal
Affiliation:
Keywords:
Calcitonin gene-related peptide, calcitonin receptor-like receptor, class B GPCR, docking, G-protein coupled
receptor, migraine.
Abstract: Class B G-protein coupled receptors are involved in a wide variety of diseases and are a major focus in drug
design. Migraines are a common problem, and one of their major causative agents is the class B G-protein coupled
receptor, Calcitonin gene-related peptide (CGRP) receptor, a target for competitive drug discovery. The calcitonin
receptor-like receptor generates complexes with a receptor activity-modifying protein, which determines the type of
receptor protein formed. The CGRP receptor comprises a complex formed from the calcitonin receptor-like receptor and
receptor activity-modifying protein 1. In this study, an in silico docking approach was used to target the calcitonin
receptor-like receptor in the bound form with receptor activity-modifying protein 1 (CGRP receptor), as well as in the
unbound form. In both cases, the resulting inhibitors bound to the same cavity of the calcitonin receptor-like receptor. The
twelve evaluated compounds were competitive inhibitors and showed efficient inhibitory activity against the CGRP
receptor and Calcitonin receptor-like receptor. The two studied quinoline derivatives demonstrated potentially ideal
inhibitory activity in terms of binding interactions and low range nano-molar inhibition constants. These compounds
could prove helpful in designing drugs for the effective treatment of migraines. We propose that quinoline derivatives
possess inhibitory activity by disturbing CGRP binding in the trigeminovascular system and may be considered for further
preclinical appraisal for the treatment of migraines.
