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

Vivek Pandey; Garima Tripathi; Dhruv Kumar; Abhijeet Kumar; Pawan K Dubey

doi:10.1016/j.heliyon.2020.e04397

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

Heliyon. 2020 Jul 14;6(7):e04397. doi: 10.1016/j.heliyon.2020.e04397. eCollection 2020 Jul.

Authors

Vivek Pandey¹, Garima Tripathi², Dhruv Kumar³, Abhijeet Kumar⁴, Pawan K Dubey¹

Affiliations

¹ Centre for Genetic Disorder, Banaras Hindu University, Varanasi, U.P., India.
² Department of Chemistry, T. N. B. College, TMBU, Bhagalpur, Bihar, India.
³ Amity Institute of Molecular Medicine & Stem Cell Research, Amity University Uttar Pradesh, Noida, India.
⁴ Department of Chemistry, School of Physical Sciences, Mahatma Gandhi Central University, Bihar, India.

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.

Keywords: Apoptosis; Bioinformatics; Biological sciences; Cell biology; Chemistry; MDA-MB-231; Molecular docking; Organic chemistry; Pharmaceutical chemistry; Pyrazole; Reactive oxygen species.