Screening and Validation of Chalcone and Chalcone Derivatives against Lung Cancer Target Protein Anaplastic Lymphoma Kinase (ALK) Using Molecular Modeling Approach
Using extensive in silico analysis, the current study explores chalcone and its synthetic chalcone derivatives (CD1 to CD15) as possible anticancer agents against lung cancer target proteins. Molecular docking research revealed significant binding affinities; docking scores ranging from -6.3 to -9.9 kcal/mol. CD12 chalcone derivative showed the highest docking score (-9.9 kcal/mol) among the substances that were tested against the target protein Anaplastic Lymphoma Kinase (ALK) (PDB ID 7R7K) through its stable hydrogen bonds and non-bonded interactions with significant amino acid residues of target protein. Next to CD12 chalcone derivative, naringenin chalcone and CD15 scores higher in molecular docking analysis. Guidelines for drug-likeness screening by Lipinski, Ghose, Veber, Egan, and Muegge confirmed that most derivatives including CD12, naringenin chalcone and CD15 had good oral bioavailability and acceptable physicochemical properties. The ADMET prediction, which demonstrated minimal hepatotoxicity, low cardiotoxicity, restricted efflux activity, and excellent intestinal absorption, supported their pharmacokinetic acceptability. Bioactivity score analysis revealed that CD3 and CD12 were promising GPCR ligands and protease inhibitors, suggesting the possibility of multi-target binding. Density Functional Theory (DFT) studies showed that CD12 and CD3 had higher softness and smaller energy gaps, suggesting greater chemical reactivity and biological efficiency. According to overall computational results, CD12 and CD3 are lead chalcone derivatives with advantageous pharmacokinetic, electrical, and bioactivity properties. Additional in vitro and in vivo testing is required to ascertain these compounds therapeutic potential in the treatment of lung cancer.
