Potential new antitumor agents from an innovative combination of demethylcantharidin, a modified traditional Chinese medicine, with a platinum moiety

被引：90

作者：

Ho, YP ^{[1
]}

To, KKW

Au-Yeung, SCF

Wang, XN

Lin, G

Han, XW

机构：

[1] Chinese Univ Hong Kong, Sch Pharm, Shatin, Hong Kong, Peoples R China

[2] Chinese Univ Hong Kong, Dept Pharmacol, Fac Med, Shatin, Hong Kong, Peoples R China

[3] Chinese Univ Hong Kong, Dept Chem, Fac Sci, Shatin, Hong Kong, Peoples R China

[4] Chinese Acad Sci, Dalian Inst Chem Phys, State Key Lab Catalysis, Dalian 116023, Peoples R China

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2001年 / 44卷 / 13期

关键词：

D O I：

10.1021/jm000476t

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A combination of demethylcantharidin, a modified component of a traditional Chinese medicine (TCM), with a platinum moiety has produced a series of TCM-based platinum compounds [Pt(C8H8O5)(NH2R)(2)] 1-5, which demonstrate selective cytotoxicity toward SK-Hep-l (human liver) cell line, and circumvention of cross-resistance. The inclusion of demethylcantharidin rendered the compounds highly active as protein phosphatase (PP2A) inhibitors. The new TCM-Pt compounds may possess a novel dual mechanism of antitumor action: inhibition of PP2A and platination of DNA.

引用

页码：2065 / 2068

页数：4

共 23 条

[1]

ALLEY MC, 1988, CANCER RES, V48, P589

[2] Reversible protein phosphorylation modulates nucleotide excision repair of damaged DNA by human cell extracts [J].

Ariza, RR ;

Keyse, SM ;

Moggs, JG ;

Wood, RD .

NUCLEIC ACIDS RESEARCH, 1996, 24 (03) :433-440

[3]

BUNGO M, 1990, CANCER RES, V50, P2549

[4] CISPLATIN METABOLITES IN PLASMA, A STUDY OF THEIR PHARMACOKINETICS AND IMPORTANCE IN THE NEPHROTOXIC AND ANTITUMOUR ACTIVITY OF CISPLATIN [J].

DALEYYATES, PT ;

MCBRIEN, DCH .

BIOCHEMICAL PHARMACOLOGY, 1984, 33 (19) :3063-3070

[5] ENHANCED DNA-REPAIR AS A MECHANISM OF RESISTANCE TO CIS-DIAMMINEDICHLOROPLATINUM(II) [J].

EASTMAN, A ;

SCHULTE, N .

BIOCHEMISTRY, 1988, 27 (13) :4730-4734

[6] CANTHARIDIN POISONING ASSOCIATED WITH SPECIFIC BINDING-SITE IN LIVER [J].

GRAZIANO, MJ ;

WATERHOUSE, AL ;

CASIDA, JE .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1987, 149 (01) :79-85

[7]

GRAZIANO MJ, 1988, MOL PHARMACOL, V33, P706

[8]

HABIG WH, 1974, J BIOL CHEM, V249, P7130

[9] EFFECTS OF CIS-MALONATO-DIAMMINO PLATINUM(II) ON P-388 LYMPHOCYTIC-LEUKEMIA CELL-METABOLISM [J].

HALL, IH ;

HOLSHOUSER, MH ;

LOEFFLER, LJ .

JOURNAL OF PHARMACEUTICAL SCIENCES, 1980, 69 (10) :1160-1163

[10] PRECLINICAL STUDIES IDENTIFYING CARBOPLATIN AS A VIABLE CISPLATIN ALTERNATIVE [J].

HARRAP, KR .

CANCER TREATMENT REVIEWS, 1985, 12 :21-33

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