Design and Development of Halogenated Chalcone Derivatives as Potential Anticancer Agents

Purpose: To design and develop halogenated chalcone derivatives and evaluate them as anticancer agents using different cancer cell lines. Methods: Based on in silico design and docking on known target, crystal structure of the complex of interleukin-1beta converting enzyme (ICE) with a peptide based inhibitor, (3S)-N-Methanesulfonyl-3-({1-[N-(2-naphtoyl)-l-valyl]-l-prolyl}amino)-4-oxobutanamide (1BMQ), novel halogenated chalcone derivatives were designed (7a-h) employing LigandFit module of Accelrys (Discovery Studio, 2.1 version). Standard protocols for ligand and protein preparation were employed and their binding orientation validated using (3S)-N-Methanesulfonyl-3-({1-[N-(2-naphtoyl)-l-valyl]-l-prolyl}amino)-4-oxobutanamide (MNO 601), a caspase inhibitor as reference standard. Energy minimized conformers with best dock scores were considered for the identification of interacting amino acid residues with ligands. Selected derivatives were synthesized and analyzed by melting point, 1H NMR, IR and mass spectroscopy. Their evaluation for anticancer activity was carried out using adriamycin, paclitaxel and 5-fluorouracil as reference standards on prostrate (PC-3), colon (COLO-205), ovary (OVCAR-5), live