Synthesis and cytotoxicity of A-homo-lactam derivatives of cholic acid and 7-deoxycholic acid

被引：46

作者：

Huang, Yanmin ^{[1
,2
]}

Chen, Sijing ^{[2
]}

Cui, Jianguo ^{[2
]}

Gan, Chunfang ^{[2
]}

Liu, Zhiping ^{[2
]}

Wei, Yingliang ^{[3
]}

Song, Huachan ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Sch Chem & Chem Engn, Guangzhou 510275, Guangdong, Peoples R China

[2] Guangxi Teachers Educ Univ, Coll Chem & Life Sci, Nanning 530001, Peoples R China

[3] Guangxi Anal Testing Ctr, Nanning 530022, Peoples R China

来源：

STEROIDS | 2011年 / 76卷 / 07期

关键词：

Cholic acid lactam; Deoxycholic acid lactam; Synthesis; Cytotoxicity; AZA-STEROIDAL ESTERS; AGENTS STRUCTURE/ACTIVITY; OXIMES;

D O I：

10.1016/j.steroids.2011.03.009

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Using cholic acid and deoxycholic acid as starting materials, a series of 3-aza-A-homo-4-one bile acid and 7-deoxycholic acid derivatives were synthesized by the esterification, oxidation, reduction, oximation and Beckman rearrangement etc. The cytotoxicity of the synthesized compounds against MGC 7901 (human ventriculi carcinoma cell line), hela (human cervical carcinoma cell line), SMMC 7404 (human liver carcinoma cell line) were investigated. The results showed that bile acid and 7-deoxycholic-acid derivatives with 3-aza-A-homo-4-one configuration bearing a 6-hydroximino or 12-hydroximino group displayed a distinct cytotoxicity to Hela tumor cell line. In particular, the IC50 values of the compounds 6 and 13 were 14.3 and 24.3 mu mol/L against Hela human tumor cell line respectively. The information obtained from the studies may be useful for the design of novel chemotherapeutic drugs. (C) 2011 Elsevier Inc. All rights reserved.

引用

页码：690 / 694

页数：5

共 18 条

[1] ANTI-TUMOR ACTIVITY OF HOMO-AZA-STEROIDAL ESTERS OF [PARA-[BIS(2-CHLOROETHYL)AMINO]PHENYL]ACETIC ACID AND [PARA-[BIS(2-CHLOROETHYL)AMINO]PHENYL]BUTYRIC ACID [J].

CATSOULACOS, P ;

POLITIS, D ;

WAMPLER, GL .

CANCER CHEMOTHERAPY AND PHARMACOLOGY, 1983, 10 (02) :129-132

[2]

CATSOULACOS P, 1993, ANTICANCER RES, V13, P1203

[3]

[陈思静 Chen Sijing], 2010, [化学研究与应用, Chemical Research and Application], V22, P848

[4] Synthesis of polyhydroxysterols (I):: synthesis of 24-methylenecholest-4-en-3β,6β-diol, a cytotoxic natural hydroxylated sterol [J].

Cui, JG ;

Zeng, LM ;

Su, JY ;

Lu, WG .

STEROIDS, 2001, 66 (01) :33-38

[5] Synthesis and evaluation of some steroidal oximes as cytotoxic agents: Structure/activity studies (I) [J].

Cui, Jian-Guo ;

Fan, Lei ;

Huang, Li-Liang ;

Liu, Hong-Li ;

Zhou, Ai-Min .

STEROIDS, 2009, 74 (01) :62-72

[6] Synthesis and evaluation of some steroidal oximes as cytotoxic agents: Structure/activity studies (II) [J].

Cui, Jianguo ;

Fan, Lei ;

Huang, Yanmin ;

Xin, Yi ;

Zhou, Aimin .

STEROIDS, 2009, 74 (12) :989-995

[7] A synthetic ionophore that recognizes negatively charged phospholipid membranes [J].

Deng, G ;

Dewa, T ;

Regen, SL .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1996, 118 (37) :8975-8976

[8] Novel modified steroid derivatives of androstanolone as chemotherapeutic anti-cancer agents [J].

El-Far, Mohamed ;

Elmegeed, Gamal A. ;

Eskander, Emad F. ;

Rady, Hanaa M. ;

Tantawy, Mohamed A. .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2009, 44 (10) :3936-3946

[9] Antimicrobial activities of squalamine mimics [J].

Kikuchi, K ;

Bernard, EM ;

Sadownik, A ;

Regen, SL ;

Armstrong, D .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1997, 41 (07) :1433-1438

[10] Rational design, synthesis, and in vivo evaluation of the antileukemic activity of six new alkylating steroidal esters [J].

Koutsourea, Anna I. ;

Fousteris, Manolis A. ;

Arsenou, Evagelia S. ;

Papageorgiou, Athanasios ;

Pairas, George N. ;

Nikolaropoulos, Sotiris S. .

BIOORGANIC & MEDICINAL CHEMISTRY, 2008, 16 (09) :5207-5215

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