Design, synthesis, <i>in vitro</i>, and <i>in silico</i> studies of novel isatin-hybrid hydrazones as potential triple-negative breast cancer agents

Abstract

Recent advances in cancer therapy have been made possible by monoclonal antibodies, domain antibodies, antibody drug conjugates, <i>etc.</i> The most impact has come from controlling cell cycle checkpoints through checkpoint inhibitors. This manuscript explores the potential of a series of novel <i>N</i>-benzyl isatin based hydrazones (5-25), which were synthesized and evaluated as anti-breast cancer agents. The synthesized hydrazones of <i>N</i>-benzyl isatin were screened <i>in vitro</i> against two cell lines, the MDA-MB-231 breast cancer cell line and the MCF-10A breast epithelial cell line. The results indicated that all compounds showed great potential against the triple-negative MDA-MB-231 breast cancer cell line. Compound 23 with nitro substitution at the 4th position of the phenyl ring exhibited significant antiproliferative potential for the MDA-MB-231 with an IC₅₀ value of 15.8 ± 0.6 μM. Molecular dynamics and molecular docking simulations were performed to get a deeper understanding of the interactions between the synthesized compounds and cancer cells.