Halogen substituted aurones as potential apoptotic agents: synthesis, anticancer evaluation, molecular docking, ADMET...

Area of Science:

• Medicinal Chemistry
• Pharmacology
• Computational Chemistry

Background:

• Aurone derivatives are explored for their potential biological activities.
• Cancer remains a significant global health challenge, necessitating novel therapeutic agents.
• Targeting specific cancer cell lines like MCF-7 is crucial for developing effective treatments.

Purpose of the Study:

• To synthesize and evaluate halogen-substituted aurone derivatives for antiproliferative activity.
• To identify potent anticancer compounds against the NCI 60 cancer cell line panel.
• To investigate the mechanism of action, including cell cycle effects and in silico properties.

Main Methods:

• Synthesis of halogen-substituted aurone derivatives (2a-k).
• In vitro antiproliferative assays against the NCI 60 cancer cell line panel.
• Apoptotic assays to analyze cell cycle progression (G0/G1, G2/M, S phases).
• In silico studies including molecular docking, ADME, toxicity prediction, MESP, and DFT.

Main Results:

• Most synthesized aurone derivatives showed promising activity against the MCF-7 cell line.
• Compound 2e exhibited significant anticancer activity against MCF-7 cells (84.98% inhibition at 10 μM, IC50 = 8.157 ± 0.713 μM).
• Compound 2e induced cell cycle arrest at the S phase and disrupted the G0/G1 and G2/M phases in MCF-7 cells.
• In silico studies revealed good docking scores for all derivatives, with MESP and DFT results supporting experimental findings.

Conclusions:

• Halogen-substituted aurone derivatives possess significant antiproliferative potential, especially against the MCF-7 cell line.
• Compound 2e is a promising candidate for further anticancer drug development due to its efficacy and cell cycle disruptive properties.
• Computational studies complement experimental data, aiding in understanding structure-activity relationships and guiding future research.