Synthesis of derivatives of NK109, 7-OH benzo[c]phenanthridine alkaloid, and evaluation of their cytotoxicities and reduction-resistant properties

被引：105

作者：

Nakanishi, T ^{[1
]}

Masuda, A ^{[1
]}

Suwa, M ^{[1
]}

Akiyama, Y ^{[1
]}

Hoshino-Abe, N ^{[1
]}

Suzuki, M ^{[1
]}

机构：

[1] Nippon Kayaku Co Ltd, Pharmaceut Grp, Kita Ku, Tokyo 1158588, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2000年 / 10卷 / 20期

关键词：

D O I：

10.1016/S0960-894X(00)00467-4

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The N-5-C-6 double bond of NK109 (an antitumor benzo[c]phenanthridine alkaloid) is easily reduced under biological environment. To suppress the inactivation caused by reduction, we synthesized 5-, 6-, and 8-substituted NK109. 5-Substituted derivatives (4a-c) were reduced more easily than NK109. 6-Substituted ones (10a-f) inhibited biological reduction, but showed weak cytotoxic activity. 8-O-Substituted ones (13a-h), especially 8-O-hydroxyethyl NK109 (13d), suppressed biological reduction and exhibited strong cytotoxic activity. (C) 2000 Elsevier Science Ltd. All rights reserved.

引用

页码：2321 / 2323

页数：3

共 11 条

[1] A topoisomerase II inhibitor, NK109, induces DNA single- and double-strand breaks and apoptosis
Fukuda, M
Inomata, M
Nishio, K
Fukuoka, K
Kanzawa, F
Arioka, H
Ishida, T
Fukumoto, H
Kurokawa, H
Oka, M
Saijo, N
[J]. JAPANESE JOURNAL OF CANCER RESEARCH, 1996, 87 (10): : 1086 - 1091
[2] Kabasawa T., 1996, Proceedings of the American Association for Cancer Research Annual Meeting, V37, P427
[3] Anti-tumour activities of a new benzo[c]phenanthridine agent, 2,3-(methylenedioxy)-5-methyl-7-hydroxy-8-methoxybenzo[c]phenanthridinium hydrogensulphate dihydrate (NK109), against several drug-resistant human tumour cell lines
Kanzawa, F
Nishio, K
Ishida, T
Fukuda, M
Kurokawa, H
Fukumoto, H
Nomoto, Y
Fukuoka, K
Bojanowski, K
Saijo, N
[J]. BRITISH JOURNAL OF CANCER, 1997, 76 (05) : 571 - 581
[4] PURIFICATION OF NADPH-LINKED ALPHA,BETA-KETOALKENE DOUBLE-BOND REDUCTASE FROM RAT-LIVER
KITAMURA, S
TATSUMI, K
[J]. ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1990, 282 (01) : 183 - 187
[5] Synthesis of NK109, an anticancer benzo[c]phenanthridine alkaloid
Nakanishi, T
Suzuki, M
Mashiba, A
Ishikawa, K
Yokotsuka, T
[J]. JOURNAL OF ORGANIC CHEMISTRY, 1998, 63 (13) : 4235 - 4239
[6] Structural considerations of NK109, an antitumor benzo[c]phenanthridine alkaloid
Nakanishi, T
Suzuki, M
Saimoto, A
Kabasawa, T
[J]. JOURNAL OF NATURAL PRODUCTS, 1999, 62 (06): : 864 - 867
[7] Synthesis and cytotoxic activities of a new benzo[c]phenanthridine alkaloid, 7-hydroxynitidine, and some 9-oxygenated benzo[c]phenanthridine derivatives
Nakanishi, T
Suzuki, M
[J]. ORGANIC LETTERS, 1999, 1 (07) : 985 - 988
[8] SOME STRUCTURAL RELATIONSHIPS AMONG CYTOTOXIC AND ANTITUMOR BENZOPHENANTHRIDINE ALKALOID DERIVATIVES
STERMITZ, FR
LARSON, KA
KIM, DK
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1973, 16 (08) : 939 - 940
[9] TAMURA T, 1999, 58 ANN M JAP CANC, pP13
[10] ANTIMICROTUBULE PROPERTIES OF BENZOPHENANTHRIDINE ALKALOIDS
WOLFF, J
KNIPLING, L
[J]. BIOCHEMISTRY, 1993, 32 (48) : 13334 - 13339

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