Molecular Design, Synthesis and Evaluation of 2,3-Diarylquinoxalines as Estrogen Receptor Ligands

Autor(es)

Sangi, Diego P. ^{[1, 2]} ; Cominetti, Marcia R. ^[3] ; Becceneri, Amanda B. ^[3] ; Resende, Flavia A. ^[4] ; Varanda, Eliana A. ^[4] ; Montanari, Carlos A. ^[5] ; Paixao, Marcio W. ^[1] ; Correa, Arlene G. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Carlos, Dept Quim, BR-13565905 Sao Carlos, SP - Brazil

^[2] Univ Fed Fluminense, Inst Ciencias Exatas, BR-27213145 Volta Redonda, RJ - Brazil

^[3] Univ Fed Sao Carlos, Dept Gerontol, BR-13565905 Sao Carlos, SP - Brazil

^[4] Univ Estadual Paulista, Fac Ciencias Farmaceut Araraquara, Dept Ciencias Biol, BR-14801902 Araraquara, SP - Brazil

^[5] Univ Sao Paulo, Inst Quim Sao Carlos, BR-13566590 Sao - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Medicinal Chemistry; v. 11, n. 8, p. 736-746, 2015.
• Citações Web of Science: 0

Resumo

Selective Estrogen Receptor Modulators (SERMs) are characteristically capable of being antagonist and agonist of estrogen receptors and, therefore, they can inhibit or stimulate estrogen production in different tissues. Aiming to contribute to the identification of new synthetic SERMs candidates, the basic skeletons of raloxifene and tamoxifene were used as model. Here of, a set of 2,3-diaryl-quinoxalines having 2-(piperidin-1-yl) ethanol in the side chain have been synthesized and evaluated against human mammary carcinoma cells estrogen dependent (MCF-7), as well as in recombinant yeast assays (RYA) expressing estrogen receptor. Compound LSPN332 showed 40% inhibition of MCF-7 and EC50= 290.6 mu M in RYA. The efficient synthesis of 2,3-diarylquinoxalines represents an excellent opportunity to identify new SERMs, and should therefore be of interest to the medicinal chemistry community. (AU)

• Processo FAPESP: 13/07600-3 - CIBFar - Centro de Inovação em Biodiversidade e Fármacos
• Beneficiário: Glaucius Oliva
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 11/01893-3 - Otimização de agentes tripanossomatídeos por integração de ensaios in silico, biocalorimétricos e celulares
• Beneficiário: Carlos Alberto Montanari
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/50680-8 - Derivados de quinoxalinas como fármacos antiparasitários: prova de conceito
• Beneficiário: Arlene Gonçalves Corrêa
• Modalidade de apoio: Auxílio à Pesquisa - Parceria para Inovação Tecnológica - PITE