ANTITUMOR AGENTS .123. SYNTHESIS AND HUMAN DNA TOPOISOMERASE-II INHIBITORY ACTIVITY OF 2'-CHLORO DERIVATIVES OF ETOPOSIDE AND 4-BETA-(ARYLAMINO)-4'-O-DEMETHYLPODOPHYLLOTOXINS

被引：32

作者：

HU, H

WANG, ZQ

LIU, SY

CHENG, YC

LEE, KH

机构：

[1] UNIV N CAROLINA,SCH PHARM,DIV MED CHEM & NAT PROD,NAT PROD LAB,CHAPEL HILL,NC 27599

[2] YALE UNIV,SCH MED,DEPT PHARMACOL,NEW HAVEN,CT 06510

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1992年 / 35卷 / 05期

关键词：

D O I：

10.1021/jm00083a009

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The 2'-chloro derivatives of etoposide and 4-beta-(arylamino)-4'-O-demethylpodophyllotoxins have been synthesized and evaluated for their inhibitory activity against the human DNA topoisomerase II as well as for their activity in causing cellular protein-linked DNA breakage. The results showed that none of the compounds are active as a result of the C-2' chloro substitution on ring E. This would suggest that the free rotation of ring E is essential for the aforementioned enzyme inhibitory activity. In addition, these 2'-chloro derivatives showed no significant cytotoxicity (KB).

引用

页码：866 / 871

页数：6

共 19 条

[1] AYRES DC, 1982, CANCER CHEMOTH PHARM, V7, P99
[2] CHEN GL, 1984, J BIOL CHEM, V259, P3560
[3] CREAVEN PJ, 1982, CANCER CHEMOTH PHARM, V7, P133
[4] DOW LW, 1983, CANCER RES, V43, P5699
[5] EVANS WE, 1982, CANCER CHEMOTH PHARM, V7, P147
[6] INVITRO METABOLISM OF ETOPOSIDE (VP-16-213) BY LIVER-MICROSOMES AND IRREVERSIBLE BINDING OF REACTIVE INTERMEDIATES TO MICROSOMAL PROTEINS
HAIM, N
NEMEC, J
ROMAN, J
SINHA, BK
[J]. BIOCHEMICAL PHARMACOLOGY, 1987, 36 (04) : 527 - 536
[7] PEROXIDATIVE FREE-RADICAL FORMATION AND O-DEMETHYLATION OF ETOPOSIDE(VP-16) AND TENIPOSIDE(VM-26)
HAIM, N
ROMAN, J
NEMEC, J
SINHA, BK
[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1986, 135 (01) : 215 - 220
[8] JARDINE I, 1980, ANTICANCER AGENTS BA, P323
[9] ANTITUMOR AGENTS .111. NEW 4-HYDROXYLATED AND 4-HALOGENATED ANILINO DERIVATIVES OF 4'-DEMETHYLEPIPODOPHYLLOTOXIN AS POTENT INHIBITORS OF HUMAN DNA TOPOISOMERASE-II
LEE, KH
BEERS, SA
MORI, M
WANG, ZQ
KUO, YH
LI, L
LIU, SY
CHANG, JY
HAN, FS
CHENG, YC
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1990, 33 (05) : 1364 - 1368
[10] ANTITUMOR AGENTS .107. NEW CYTO-TOXIC 4-ALKYLAMINO ANALOGS OF 4'-DEMETHYL-EPIPODOPHYLLOTOXIN AS INHIBITORS OF HUMAN DNA TOPOISOMERASE-II
LEE, KH
IMAKURA, Y
HARUNA, M
BEERS, SA
THURSTON, LS
DAI, HJ
CHEN, CH
LIU, SY
CHENG, YC
[J]. JOURNAL OF NATURAL PRODUCTS, 1989, 52 (03): : 606 - 613

← 1 2 →