Design, synthesis, anticancer activity and molecular docking analysis of novel dinitrophenylpyrazole bearing 1,2,3-triazoles

Abstract

• Novel dinitrophenylpyrazole bearing 1,2,3-triazol molecular hybrids were reported. • Its structure elucidation was established via different spectroscopic techniques. • Synthesized compounds were evaluated anti-cancer activity ( in vitro ) against three human cell lines. • Compounds 9e, 9f , and 9 h showed the high potency growth inhibitory activity against the HeLa cell line. • Binding interaction were also validated with molecular docking studies. A novel series of dinitrophenylpyrazole bearing triazole scaffolds were designed and synthesized with appreciable yields. The structures of all the target molecules ( 9a–j ) were confirmed and characterized by 1 H NMR, 13 C NMR, FT-IR and HR-MS spectral techniques. These novel molecules were tested for their anti-cancer activity ( in vitro) using three tumor cell lines indicating breast adenocarcinoma (MCF-7), cervical carcinoma (HeLa), and human epithelial colorectal adenocarcinoma (Caco-2) via the MTT approach. Compounds 9e, 9f, and 9 h showed the high potency growth inhibitory activity against the HeLa cell line (IC 50 = 4.0 μM, 5.0 μM and 6.0 μM) higher than that of Combretastatin-A4 (IC 50 = 9.0 μM) as reference drug. Besides, compound 9 h was found to be highly potent against MCF-7 cell line IC 50 value of 8.0 μM. Additionally, in this manuscript, the structure-activity relationship (SAR) analysis is reported. Molecular docking studies also confirm the experimental findings and explains the most probable interaction pattern.