Toward chelerythrine optimization: Analogues designed by molecular simplification exhibit selective growth inhibition in non-small-cell lung cancer cells

Author(s)

Yang, Rosania ; Tavares, Mauricio T. ; Teixeira, Sarah F. ; Azevedo, Ricardo A. ; Pietro, Diego C. ; Fernandes, Thais B. ; Ferreira, Adilson K. ; Trossini, Gustavo H. G. ; Barbuto, Jose A. M. ; Parise-Filho, Roberto

• Document type: Journal article
• Source: Bioorganic & Medicinal Chemistry; v. 24, n. 19, p. 4600-4610, OCT 1 2016.
• Web of Science Citations: 2

Abstract

A series of novel chelerythrine analogues was designed and synthesized. Antitumor activity was evaluated against A549, NCI-H1299, NCI-H292, and NCI-H460 non-small-cell lung cancer (NSCLC) cell lines in vitro. The selectivity of the most active analogues and chelerythrine was also evaluated, and we compared their cytotoxicity in NSCLC cells and non-tumorigenic cell lines, including human umbilical vein endothelial cells (HUVECs) and LL24 human lung fibroblasts. In silico studies were performed to establish structure-activity relationships between chelerythrine and the analogues. The results showed that analogue compound 3f induced significant dose-dependent G(0)/G(1) cell cycle arrest in A549 and NCI-H1299 cells. Theoretical studies indicated that the molecular arrangement and electron characteristics of compound 3f were closely related to the profile of chelerythrine, supporting its activity. The present study presents a new and simplified chelerythrinoid scaffold with enhanced selectivity against NSCLC tumor cells for further optimization. (C) 2016 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 13/18160-4 - Novel anticancer candidates: design, synthesis, antitumoral activity and mode of action of novel capsaicinoids and capsinoids analogues
• Grantee: Roberto Parise Filho
• Support Opportunities: Regular Research Grants