Title:Synthesis and Evaluation of a New Series of Arylidene Indanones as Potential Anticancer Agents
Volume: 18
Issue: 10
Author(s): Ahmet Özdemir*, Sevtem Gökbulut, Belgin Sever, Gülşen A. Çiftçi and Mehlika D. Altıntop
Affiliation:
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskisehir,Turkey
Keywords:
Chalcone, indanone, anticancer activity, apoptosis, caspase-3, DNA synthesis inhibition.
Abstract: 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.
