Identification of chrysin derivatives anticancer potential in MCF7 cells: biological insights and in silico evaluation.

Abstract

Aim: To synthesize and evaluate the anticancer potential and mechanism of a naturally occurring compound, chrysin derivatives.

Materials & methods: A series of 7-substituted phenyl pyrano derivatives of chrysin (3a-k) were synthesized by Michael-type addition reaction and their structures were elucidated using spectroscopic techniques, such as FT-IR, H¹ NMR, C¹³ NMR, and MS. In vitro anticancer and cytotoxicity effects were evaluated using MCF7 and mesenchymal stem cells (MSCs). Apoptosis mechanism was evaluated through the expression of pro- and anti-apoptotic proteins, for instance, Bax, Bcl-2, p53, and p21, and the binding score and stability was computed using AutoDock Vina and GROMACS. In silico ADMET analysis was performed via web-based tools like Swiss ADME, pkCSM, ADMETlab 2.0, PreADMET, ProTox II, and Molinspiration.

Results: Structure activity relationship (SAR) analysis revealed that the 4-hydroxy substituted phenyl derivative (3h) is important for anticancer activity. 3 h enhanced the expression of Bax, Bcl-2, and p53 while decreases in the expression of oncogene p21 at 16.5 µM concentration showed superior activity to standard carboplatin and was found safe up to 77.95 μM. All the derivatives displayed favorable pharmacokinetic and drug-like properties.

Conclusion: The 4-hydroxy substituted phenyl derivative (3h) spectacled enhanced anticancer and safety profile along with considerable pharmacokinetic parameters.