Comparative study of novel synthetic cyanochalcone derivatives versus curcumin as antineoplastic agents

Abstract

Background: the demand for new efficient antineoplastic compounds to lessen the burden of cancer is constantly growing; with recent approaches seeking to develop new efficient natural or synthetic chemotherapeutic agents with fewer side effects. Aim: the present study was conducted aiming to screen in vitro the potential cytotoxic effects of a series of newly synthesized cyanochalcones versus that of the widely used natural compound curcumin. In addition, the interactions of these compounds with some cellular markers has been tested in silico through molecular docking approaches. Materials and methods: MTT assay was used to confirm the antiproliferative effects of cyanochalcone derivative 1 (CN ch1) and 5 (CN ch5) from the series of novel chalcones, against lung cancer (A549), colorectal cancer (HCT-116), hepatocellular carcinoma (HepG2) and prostate cancer (PC3) cell lines, in parallel with normal human lung cells (WI-38); while dose response curves and IC50 were calculated using GraphPad Prism. Molecular docking using softwares UCSF Chimera and Pymol was then performed to understand molecular interactions of the synthetic compounds. Results and discussion: data from CN ch1 has shown IC50 values of 149.1 g/ml, 778 g/ml, 241.1 g/ml, 42.68 g/ml against A549, HCT-116, HepG2 and PC3 cancer cell lines respectively, while exhibiting no cytotoxic effects towards WI-38. Similarly, CN ch5 has shown IC50 values of 199.2 g/ml, 1615 g/ml, 77.1 g/ml, 186.8 g/ml and 191.7 g/ml; while curcumin exhibited IC50 values of 40.1 g/ml, 126.7 g/ml, 31.1 g/ml, 31.61 g/ml and 36.47 g/ml. Among the tested compounds, curcumin thus exhibited highest inhibition of cell viability and lower IC50 values, reflecting the validity of using natural compounds to treat cancer instead of synthetic ones. Nonetheless, docking studies have also proved the potent binding affinity of the cyanochalcone derivatives towards selected receptors, with different binding free energies of -11.3, -11.2, -10.7 and 10.3 Kcal/mol for MMP-9, iNOS, AKT2