Multicomponent synthesis of novel spiro-indoline-3,4'-pyran derivatives: in silico and in vitro study.

In this work, a series of 15 novel spiro-indoline-3,4'-pyrans (4) were synthesized by a simple multi-component reaction. Several spectroscopic methods were used to fully characterize the produced compounds 4a-o. Compounds 4e, and 4f demonstrated anticancer effects on the MCF-7 breast cancer cell line (IC50 = 9.19 ± 1.29 µM and 2.93 ± 1.79 µM, respectively) by MTT assay. In addition, MCF-7 cells treated with compounds 4e and 4f showed a lower number of colonies in the colony formation assay than the control group. Compounds 4e and 4f demonstrated significant apoptotic effects on MCF-7 cells with a percentage of apoptosis (early and late) of 53.1% and 46%, respectively. Finally, the best docked pose of compounds 4e and 4f against CDK2 was selected for further molecular dynamics (MD) simulation studies. Our data suggest that spiro-indoline-3,4'-pyran is a suitable core for optimization to identify novel anticancer agents.