Current basis for discovery and development of aryl hydrocarbon receptor antagonists for experimental and therapeutic use in atherosclerosis

Autor(es)

Pernomian, Larissa ^[1] ; da Silva, Carlos H. T. P. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Computat Lab Pharmaceut Chem, BR-14040903 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo de Revisão
• Fonte: European Journal of Pharmacology; v. 764, p. 118-123, OCT 5 2015.
• Citações Web of Science: 6

Resumo

The important role played by aryl hydrocarbon receptor activation in the pathophysiology of atherosclerosis induced by cigarette smoke exposure has spurred the clinical interest in the development of aryl hydrocarbon receptor antagonists with atheroprotective efficacy. A few aryl hydrocarbon receptor antagonists were developed but the lack of structural information regarding the receptor ligand binding domain resulted in several limitations in the pharmacological properties of these compounds including partial agonism, allosterism, non-selectivity, cytotoxicity and susceptibility to bioactivation. These limitations make the progress of preclinical and clinical assays with the available aryl hydrocarbon receptor antagonists difficult. There is a great interest in developing pure, competitive, selective, nontoxic and resistant to bioactivation aryl hydrocarbon receptor antagonists. Current technology permits he development of pharmacologically ideal antagonists based on the chemical features of the aryl hydrocarbon receptor ligand binding domain. According to these characteristics, chlorinated derivatives of trans-stilbene mew-substituted with electrophilic aromatic directing groups would be effective prototypes for pure, competitive, selective, nontoxic and resistant to bioactivation antagonists for such receptor. (C) 2015 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 14/17740-0 - Planejamento, desenvolvimento e avaliação farmacológica de novos antagonistas de receptores para hidrocarbonetos arila (AhR) candidatos a fármacos ateroprotetores
• Beneficiário: Larissa Pernomian
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs