Thioaryl naphthylmethanone oxime ether analogs as novel anticancer agents.

Employing a rational design of thioaryl naphthylmethanone oxime ether analogs containing functional properties of various anticancer drugs, a series of compounds were identified that displayed potent cytotoxicity toward various cancer cells, out of which 4-(methylthio)phenyl)(naphthalen-1-yl)methanone O-2-(diethylamino)ethyl oxime (MND) exhibited the best safety profile. MND induced apoptosis, inhibited migration and invasion, strongly inhibited cancer stem cell population on a par with salinomycin, and demonstrated orally potent tumor regression in mouse MCF-7 xenografts. Mechanistic studies revealed that MND strongly abrogated EGF-induced proliferation, migration, and tyrosine kinase (TK) signaling in breast cancer cells.