Document Report Card

ID: ALA3352791

Journal: J Med Chem

Title: Thioaryl naphthylmethanone oxime ether analogs as novel anticancer agents.

Authors: Chakravarti B, Akhtar T, Rai B, Yadav M, Akhtar Siddiqui J, Dhar Dwivedi SK, Thakur R, Singh AK, Singh AK, Kumar H, Khan K, Pal S, Rath SK, Lal J, Konwar R, Trivedi AK, Datta D, Mishra DP, Godbole MM, Sanyal S, Chattopadhyay N, Kumar A.

Abstract: 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. However, MND failed to directly inhibit EGFR or other related receptor TKs in a cell-free system. Systematic investigation of a putative target upstream of EGFR revealed that the biological effects of MND could be abrogated by pertussis toxin. Together, MND represents a new nonquinazoline potential drug candidate having promising antiproliferative activity with good safety index.

CiteXplore: 25198997

DOI: 10.1021/jm500873e