Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 19, Issue 12, Pages -Publisher
MDPI
DOI: 10.3390/ijms19123728
Keywords
cancer; HER-2; EGFR; drug design; docking; CoMFA; CoMSIA; dual inhibitor
Funding
- Sao Paulo Research Foundation (FAPESP) [2018/23903-0, 2018/06680-7, 2016/24524-7, 2016/18840-3]
- National Council for Scientific and Technological Development (CNPq)
- Coordination for the Improvement of Higher Education Personnel (CAPES)
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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.
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