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

Recent advances in cancer therapy have been made possible by monoclonal antibodies, domain antibodies, antibody drug conjugates, etc. The most impact has come from controlling cell cycle checkpoints through checkpoint inhibitors. This manuscript explores the potential of a series of novel N-benzyl isatin based hydrazones (5-25), which were synthesized and evaluated as anti-breast cancer agents. The synthesized hydrazones of N-benzyl isatin were screened in vitro 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 IC(50) 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.