The preparation of bi-functional organophosphine oxides as potential antitumor agents.
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.
Lam
Kim-Hung
KH
Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hong Kong, China. bcjoelam@inet.polyu.edu.hk
Chui
Chung-Hin
CH
Gambari
Roberto
R
Wong
Raymond Siu-Ming
RS
Cheng
Gregory Yin-Ming
GY
Lau
Fung-Yi
FY
Lai
Paul Bo-San
PB
Tong
See-Wai
SW
Chan
Kit-Wah
KW
Wong
Wai-Yeung
WY
Chan
Albert Sun-Chi
AS
Tang
Johnny Cheuk-On
JC
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D010087:Oxides / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization
D000970:Antineoplastic Agents; D009943:Organophosphorus Compounds; D010087:Oxides