Structure-guided development of Quinoline derivatives targeting kinesin spindle protein

Abstract

The kinesin Eg5 protein is a promising target for cancer therapy due to its crucial role in mitosis. This study designed and evaluated 2-((7-chloroquinolin-4-yl) amino) benzohydrazide derivatives as Eg5 inhibitors. Compounds 6d and 6e exhibited potent inhibition (IC₅₀: 1.519 ± 0.4415 μM and 0.2848 ± 0.070 μM, respectively) and significant antiproliferative activity against MCF-7 cells. Pharmacophore modeling, docking, MD simulations, and MM/GBSA analyses confirmed stable interactions within the Eg5 active site. These compounds also modulate breast cancer-related pathways, including PI3K-Akt and MAPK. These findings highlight compounds 6d and 6e as promising anticancer agents, warranting further in vivo studies to validate their therapeutic potential.