title: Quinoline derivatives: candidate drugs for a class B G-protein coupled receptor, the calcitonin gene-related peptide receptor, a cause of migraines.
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.
authors.forename: Hira
authors.initials: H
authors.lastname: Iftikhar
authors.forename: Iqra
authors.initials: I
authors.lastname: Ahmad
authors.forename: Siew H
authors.initials: SH
authors.lastname: Gan
authors.forename: Munvar M
authors.initials: MM
authors.lastname: Shaik
authors.forename: Naveed
authors.initials: N
authors.lastname: Iftikhar
authors.forename: Muhammad S
authors.initials: MS
authors.lastname: Nawaz
authors.forename: Nigel H
authors.initials: NH
authors.lastname: Greig
authors.affiliation: Metabolomics & Enzymology Unit, Fundamental and Applied Biology Group, King Fahd Medical Research Center, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia. prof.makamal@lycos.com.
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Kamal
mesh_terms: D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D020134:Catalytic Domain / Q000187:drug effects; D006801:Humans; D008881:Migraine Disorders / Q000188:drug therapy / Q000378:metabolism; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology*; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D011804:Quinolines; D018015:Receptors, Calcitonin Gene-Related Peptide; D043562:Receptors, G-Protein-Coupled