Synthesis and evaluation of tryptanthrin derivatives as promising anticancer agents: In vitro, in silico, and SAR insights

Abstract

In this study, with the aim of identifying new anticancer agents, we synthesized a series of tryptanthrin derivatives. All the synthesized compounds were investigated for their anticancer potential in-vitro, using an MTT-based assay against a panel of three different cancer cell lines (A-549, MCF-7, and MDA-MB-231). Amongst the synthesized derivatives, compound 3 showed excellent anticancer activity, with GI50 values of 5.03 ± 0.77 µM, 3.76 ± 0.55 µM, and 4.20 ± 0.50 µM against A-549, MDA-MB-231 and MCF-7 cells, respectively. Furthermore, these molecules did not show any cytotoxic effect against normal mouse embryonic fibroblast (NIH/3T3) cell lines suggesting no intrinsic cytotoxicity. In this study, ADME and toxicity profiles of the synthesized compounds were also predicted using in silico techniques. According to the findings, all of the synthesized derivatives are nontoxic and non-carcinogenic in the biological system and showed good ADME properties. Finally, potent compounds were subjected to in silico molecular docking and simulation studies were carried out against maternal embryonic leucine zipper kinase (MELK) to uncover potential protein-ligand interactions and affinity at the binding site. This study will help in the future development of novel anticancer agents.