Background: Arylidene indanones have attracted a great deal of interest due to their outstanding therapeutic applications. In particular, considerable research has pointed out the importance of arylidene indanones in the field of cancer research.
Objective: The aim of the current work was to design and synthesize arylidene indanone-based anticancer agents.
Method: New arylidene indanones were obtained via the Claisen-Schmidt condensation of 5-chloro-6-methoxy- 2,3-dihydro-1H-inden-1-one with p-substituted benzaldehyde derivatives. MTT assay was performed to evaluate their cytotoxic effects on MCF-7 human breast adenocarcinoma, HeLa human cervix carcinoma and NIH/3T3 mouse embryonic fibroblast cell lines. The most effective derivatives were evaluated for their DNA synthesis inhibitory and apoptotic effects. The most apoptotic compounds were also investigated for their effects on caspase-3 activation in HeLa cells. The binding interactions of the most effective caspase-3 activator at the active site of caspase-3 were confirmed through molecular docking studies using Schrodinger’s Maestro molecular modeling package.
Results and Conclusion: Compounds 2, 3, 4, 5, 6 and 7 exhibited selective anticancer activity against HeLa cells, whilst compounds 7 and 10 showed selective anticancer activity against MCF-7 cells. Compound 10 caused significant DNA synthesis inhibition on MCF-7 cells, whereas compound 3 caused significant DNA synthesis inhibition on HeLa cells. Compounds 2 and 3 were determined as the most apoptotic agents against HeLa cells, whereas compounds 7 and 10 showed apoptotic activity against MCF-7 cells. Besides, compound 2 was identified as the most effective compound on caspase-3 activation in HeLa cells. Docking studies showed that compound 2 interacted with the residues His121 and Tyr204 forming π-π stacking interactions.