Phenylpropiophenone derivatives as potential anticancer agents: synthesis, biological evaluation and quantitative...

Area of Science:

• Medicinal Chemistry
• Computational Chemistry
• Pharmacology

Background:

• Cancer remains a leading cause of mortality worldwide, necessitating the development of novel therapeutic agents.
• Chalcone and propafenone derivatives are classes of compounds with known biological activities, including potential anticancer effects.

Purpose of the Study:

• To synthesize and evaluate the in vitro anticancer activity of twelve novel chalcone and propafenone derivatives.
• To perform 2D and 3D Quantitative Structure-Activity Relationship (QSAR) studies to understand the structural requirements for anticancer activity.
• To identify key molecular descriptors and pharmacophores to guide the design of more potent anticancer agents.

Main Methods:

• Synthesis of twelve chalcone and propafenone derivatives.
• In vitro cytotoxicity assays against HeLa, Fem-X, PC-3, MCF-7, LS174, and K562 cancer cell lines.
• 2D-QSAR and 3D-QSAR modeling using Partial Least Squares (PLS) regression.
• Model validation using leave-one-out cross-validation and external validation.

Main Results:

• All synthesized compounds exhibited varying degrees of cytotoxic activity against the tested cancer cell lines.
• QSAR models successfully identified significant molecular descriptors and pharmacophores correlated with anticancer activity.
• Optimal 2D-QSAR and 3D-QSAR models were developed for each cell line, demonstrating good predictive potential.

Conclusions:

• The study successfully identified promising chalcone and propafenone derivatives with significant anticancer activity.
• QSAR analysis provided valuable insights into the structural features essential for enhancing anticancer efficacy against specific cancer types.
• The findings pave the way for the rational design of novel, more potent anticancer drug candidates based on chalcone and propafenone scaffolds.