Toward chelerythrine optimization: Analogues designed by molecular simplification exhibit selective growth inhibition in non-small-cell lung cancer cells |
| |
| Affiliation: | 1. Centro de Ciências Biológicas e da Saúde, Universidade Presbiteriana Mackenzie, São Paulo, Brazil;2. Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;3. Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;4. Wright State University, Dayton, OH, United States of America;5. Laboratório de Planejamento e Síntese de Substâncias Bioativas (LAPESSB), Universidade de São Paulo, São Paulo, Brazil |
| |
| 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 G0/G1 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. |
| |
| Keywords: | Chelerythrine NSCLC Molecular simplification Chelerythrine analogues |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
