Novel 3,4-diarylpyrazole as prospective anti-cancerous agents

Abstract

Cancer is a leading cause of death globally. Despite therapeutic advancements the mortality rate of cancer is continuously increasing. Thus, it is important to identify and design potential therapeutic agents which can specifically bind with most common targets of cancer and inhibit tumor progression. The present work discloses the potential therapeutic application of the novel 3,4-diaryl 1H-pyrazoles as prospective anti-cancerous agent. The in silico molecular docking studies performed with 3,4-disubstituted pyrazoles as ligand with targets including DNA, BCL-2 and F1-ATP Synthase revealed strong binding affinity with DNA (-7.5 kcal/mol), BCL-2 (-8.1 kcal/mol) and F1-ATP Synthase (-7.2 kcal/mol). Furthermore, the in silico finding was validated with the in vitro cytotoxicity assay with human breast cancer cell line (MDA-MB-231). MDA-MB-231 cells treated with 3,4-diarylpyrazole resulted in an increase in annexin-V positive cells, production of reactive oxygen species (ROS), dissipation of the mitochondrial membrane potential and activation of caspase-3. Taken together, this study demonstrate that a novel synthesized 3,4-diarylpyrazoles, showed strong binding affinity against DNA, anti-proliferative activity and executed apoptosis through ROS-dependent caspase-3-mediated mitochondrial intrinsic apoptotic pathway against MDA-MB-231 cells. These findings increase our understanding of the molecular mechanism (s) by which 3,4-diarylpyrazoles can exert their anticancer activity and may contribute towards development of novel therapeutic agent against breast cancer. © 2020 The Author(s); Pyrazole; Molecular docking; Apoptosis; Reactive oxygen species; MDA-MB-231; Chemistry; Organic chemistry; Pharmaceutical chemistry; Biological sciences; Cell biology; Bioinformatics © 2020 The Author(s)