Computational studies of new Aryl hydrocarbon receptor (AhR) antagonists, with potential atheroprotective efficacy in smokers

Abstract

Cardiovascular diseases result from atherosclerotic lesions andaccount for 31% of world mortality. One of the biggest risk factors foratherosclerosis is smoking, which accelerates the atherogenic process by activatingaryl hydrocarbon (AhR) receptors by smoke contaminants from thecigarette. These receptors belong to the bHLH / PAS protein superfamily andinduce the expression of pro-atherogenic factors, which creates a great interest ofdevelop antagonists of these receptors for atheroprotective effects insmokers. However, available AhR antagonists have serious limitations, such asallosterism, cytotoxicity, tendency to bioactivation, which prevents its evaluation inclinical trials. These difficulties are due to the limitation caused by the scarcityinformation about the ligand interaction domain of theAh. Therefore, the present theoretical project aims to: (1) introduce the student to themain computational techniques in Medicinal Chemistry; (2) plan and investigatepotential AhR antagonists, potentially non-toxic and resistant tobiotransformation through computational chemistry