Synthesis and in vitro Antiproliferative Evaluation and Molecular Docking Studies of Novel Chalcone-Phosphonates Derivatives as Anticancer Agents

Based on the wide range of pharmacological aspects related to organophosphates, a new type of chalcone-phosphonate containing derivatives were synthesized by the reaction of dialkyl phosphite and substituted chalcones using anhydrous Mg(ClO4)(2) at 80 degrees C under solvent-free conditions. The resulting compounds were evaluated for anti-proliferative activity in vitro against a panel of three human cancer cell lines: MCF7, HeLa, and A549 cell lines. Compound 3 l, 3 m, and 3 p exhibited anti-proliferative activity against MCF7 and HeLa, with IC50 values of 1.12 mu M, 1.63 mu M, 1.09 mu M and 1.29 mu M, 1.44 mu M, 2.40 mu M respectively. The molecular docking study showed that the synthesized derivatives have good binding ability in the active site of the Vaccinia H1-related (VHR) phosphatase (PDB: 3F81), PI3- kinase (PDB: 3R7Q), androgen receptor (PDB: 3V49) and VEGFR2 kinase (PDB: 3VHE). Finally, in silico pharmacokinetic (ADME) and toxicity studies revealed that compounds have the drug-like feature for the favourable bioavailability. In conclusion, this work confirmed the potency of chalcone-phosphonates derivatives for the further optimization of potential anti- proliferative agents.