1245567-49-0Relevant articles and documents
Synthesis and biological evaluation of novel 2,4′-bis substituted diphenylamines as anticancer agents and potential epidermal growth factor receptor tyrosine kinase inhibitors
Abou-Seri, Sahar Mahmoud
experimental part, p. 4113 - 4121 (2010/09/14)
Four new series of 2,4′-bis diphenylamine hydrazones 14, 2,4′-bis aminothiadiazole 16, 2,4′-bis mercaptotriazole 17-18 and 2,4′-bis mercapto-oxadiazole diphenylamine derivatives 19-20 were synthesized and evaluated for their ability to inhibit EGFR tyrosine kinase. Compound N-ethyl-5-{2-[4-(5-(ethylamino)-1,3,4-thiadiazol-2-yl)- phenylamino]phenyl}-1,3,4-thiadiazol-2-amine 16a was the most active enzyme inhibitor (98% inhibition at 10 μM). Moreover, all compounds that showed enzyme inhibition activity were tested in vitro on human breast carcinoma cell line (MCF-7) in which EGFR is highly expressed. The tested compounds exploited potent antitumor activity with IC50 values ranging 0.73-2.38 μM. Molecular modeling and docking of the synthesized compounds into the active site of EGFR kinase domain showed good agreement with the obtained biological results. The present work represents a novel class of diphenylamine based derivatives with potent cytotoxicity and promising EGFR PTK inhibition activity. Several analogues 2,4′-bis substituted diphenylamines were synthesized and evaluated as EGFR tyrosine kinase inhibitors as well as for their antiprolifertive properties on human breast cancer cell lines (MCF-7).
