Design, Synthesis and Biological Evaluation of Novel Piperidinyl Chalcones

Abstract:

Aim/Background: Chalcones are one of the important class of compounds possessing a wide range of biological properties [Dinmock 1999, Go 2005]. One of the extensive area in research on chalcones is expressed in terms of their ability to act on various cancer cell lines by a variety of molecular mechanisms. Chalcones possessing methoxy groups, a trimethoxy substituted chalcone (PGHSD 234) is the most potent chalcone with cytotoxicity comparable to the standard drugs. Materials and Methods: The antioxidant potential in terms of their free radical scavenging ability and antiproliferative activities were evaluated. Log P value and cyclic Voltammetric studies were carried out to assess their hydrophobicity and to determine their anti-oxidant potential. MTT (methyl tetrazolium) assay was performed on two cell lines including Vero and MCF-7 cell lines. Molecular docking studies were performed to assess the binding pattern of synthesized chalcones into the ATP binding site of CDK2/Cyclin A protein target. Results: The MTT assay results showed the effect of various substituents on the chalcone template that could influence their cytotoxic effect. The hydrophobicity of the synthesized compounds were reported as distribution coefficient (Log D) and all the compounds showed Log D values in the range of 1.45–4.0. The cyclic voltammetric studies revealed their irreversible oxidation potential and were found in the range of -0.400 to -0.654. Conclusion: The present study provides insight for the better understanding of mechanistic studies of N-methyl piperidinyl chalcones against anticancer targets such as CDK and aromatase identified in breast cancer.

Key words: Chalcones, Piperidinyl, Cancer, CDK2/Cyclin A, Docking.