Design, Synthesis, and Cytotoxicity of 1H‐1,2,3‐Triazole Tethered‐Benzophenone Based Derivatives as Potent Candidate Anti‐Breast Cancer Agents

Abstract

The process of developing potential anticancer molecules comprises the cautious selection of core moiety and tethering pharmacologically active chemical functionalities to biologically active pharmacophores. Here, we report a library of ten 1H‐1,2,3‐triazole tethered‐benzophenone derivatives. Protein‐ligand interaction studies through molecular docking of our synthesised compounds were carried out with a novel epigenetic oncogene‐enhancer of zeste homolog2 (EZH2). Molecular docking studies disclosed that our synthesized compounds showed potent inhibition against EZH2 and in‐vitro validation assays through MTT assay, Trypan blue dye exclusion and in‐vitro methylation assays, these studies revealed the synthesized compounds‐9 c, 9 f, 9 i showed potent inhibition on EZH2. The anticipated anti‐cancer activity of library molecules was assessed in in‐vitro against breast and lung cancer (MCF7 and A549) cell lines, supported by in‐vitro assays and molecular docking binding studies. Among all ten compounds, 9 c, 9 f, 9 i are exerted potential anti‐cancer activity against the selected cancer cell line in in‐vitro. The results were supported by in‐silico docking studies. Further validation studies in in‐vivo models will pave a way for developing potent inhibitors against breast cancer and lung cancer.

Ellagic acid: a potential inhibitor of enhancer of zeste homolog-2 and protein arginine methyltransferase-5

“…Plethora of synthetic small molecule as inhibitors of EZH2 and PRMT5 are different stages of development. (47, 77). Despite of these the advancements in therapeutic strategies and treatments lead to severe side effects in cancer patients.…”