Studies on the Dual Activity of EGFR and HER-2 Inhibitors Using Structure-Based Drug Design Techniques

Autor(es)

de Angelo, Rafaela Molina ; Almeida, Michell de Oliveira ; de Paula, Heberth ; Honorio, Kathia Maria

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 19, n. 12, p. 16-pg., 2018-12-01.

Resumo

HER-2 and EGFR are biological targets related to the development of cancer and the discovery and/or development of a dual inhibitor could be a good strategy to design an effective drug candidate. In this study, analyses of the chemical properties of a group of substances having affinity for both HER-2 and EGFR were carried out with the aim of understanding the main factors involved in the interaction between these inhibitors and the biological targets. Comparative analysis of molecular interaction fields (CoMFA) and comparative molecular similarity index analysis (CoMSIA) techniques were applied on 63 compounds. From CoMFA analyses, we found for both HER-2 (r(2) calibration = 0.98 and q(cv)(2) = 0.83) and EGFR (r(2) calibration = 0.98 and q(cv)(2) = 0.73) good predictive models. Good models for CoMSIA technique have also been found for HER-2 (r(2) calibration = 0.92 and q(cv)(2) = 0.74) and EGFR (r(2) calibration = 0.97 and q(cv)(2) = 0.72). The constructed models could indicate some important characteristics for the inhibition of the biological targets. New compounds were proposed as candidates to inhibit both proteins. Therefore, this study may guide future projects for the development of new drug candidates for the treatment of breast cancer. (AU)

• Processo FAPESP: 16/24524-7 - Análise estrutural e estudos de modelagem molecular para ligantes de origem natural e sintética relacionados a doenças negligenciadas
• Beneficiário: Kathia Maria Honorio
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/18840-3 - Aplicação de técnicas de transferência de aprendizagem e ontologias a modelos QSAR para regressão
• Beneficiário: Patrícia Rufino Oliveira
• Modalidade de apoio: Auxílio à Pesquisa - Parceria para Inovação Tecnológica - PITE
• Processo FAPESP: 18/06680-7 - Aplicação de ontologias em estudos de química medicinal computacional e relações entre estrutura química e atividade biológica
• Beneficiário: Rafaela Molina de Angelo
• Modalidade de apoio: Bolsas no Brasil - Mestrado