RESUMO
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.
Assuntos
Peptídeo Relacionado com Gene de Calcitonina/antagonistas & inibidores , Transtornos de Enxaqueca/dietoterapia , Extratos Vegetais/farmacologia , Verduras/química , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina , Simulação por Computador , Descoberta de Drogas , Humanos , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/metabolismo , Simulação de Acoplamento Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacocinética , Receptores de Peptídeo Relacionado com o Gene de Calcitonina/química , Receptores de Peptídeo Relacionado com o Gene de Calcitonina/metabolismoRESUMO
LXR (encoded by NR1H2 and 3) and FXR (known as bile acid receptor) encoded by NR1H4 (nuclear receptor subfamily 1, group H and member 4) are nuclear receptors in humans and are important regulators of bile acid production, cholesterol, fatty acid and glucose homeostasis hence responsible for liver detoxification. Several strategies for drug design with numerous ligands for this target have failed owing to the inability of the ligand to access the target/receptor or their early metabolisation. In this work, we have evaluated FXR and LXR structure bound with agonist and compared the binding energy affinity of active ligands present in live green-real veggies with reference drugs (ligands) present in the market. A high throughput screening combined with molecular docking, absorption, distribution, metabolism, excretion and toxicity (ADMET) predictions, log P values and percentage of human oral absorption value led to the identification of two compounds present in live green-real veggies with strong potential for liver detoxification.