The preparation of bi-functional organophosphine oxides as potential antitumor agents.

Kim-Hung Lam, Chung-Hin Chui, Roberto Gambari, Raymond Siu-Ming Wong, Gregory Yin-Ming Cheng, Fung-Yi Lau, Paul Bo-San Lai, See-Wai Tong, Kit-Wah Chan, Wai-Yeung Wong, Albert Sun-Chi Chan, Johnny Cheuk-On Tang

Index: Eur. J. Med. Chem. 45 , 5527-30, (2010)

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Abstract

Following our previously reported pyridinyl phosphine oxides as antitumor agents, we targeted the commercially available C(2)-axial chiral organophosphine ligand catalysts, such as 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP) 1 and 2,2',6,6'-tetramethoxy-4,4'-bis(diphenylphosphino)-3,3'-bipyridine (P-Phos) 2 as a convenient source for producing organophosphine oxides as antitumor leads. Their corresponding chiral and racemic bi-phosphine oxides 3 and 4 can be obtained easily through a simple oxidation step with hydrogen peroxide, and their antitumor activities towards human hepatocellular carcinoma Hep3B cell line were reported. We found out that compound 3 shows stronger antitumor activity than that of 4, where axial chirality cannot improve their activity. Further athymic nude mice Hep3B xenograft model demonstrates the attractive in vivo antitumor potential of 3.Copyright © 2010 Elsevier Masson SAS. All rights reserved.