IPOMEANOL ANALOGS AS CHEMOPREVENTIVE AGENTS - EFFECT ON THE IN-VITRO METABOLISM OF 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE (NNK)

被引：6

作者：

DESAI, D ^{[1
]}

NUNES, M ^{[1
]}

CHANG, L ^{[1
]}

LIN, JM ^{[1
]}

JIAO, D ^{[1
]}

AMIN, S ^{[1
]}

机构：

[1] AMER HLTH FDN,NAYLOR DANA INST DIS PREVENT,VALHALLA,NY 10595

来源：

CANCER LETTERS | 1995年 / 97卷 / 02期

关键词：

4-IPOMEANOL ANALOGS; N-NITROSAMINES; IN VITRO METABOLISM; INHIBITION;

D O I：

10.1016/0304-3835(95)03971-X

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a tobacco-specific, powerful, organospecific lung carcinogen. 4-Ipomeanol (IPO) is an investigational chemotherapeutic drug with specific toxicity towards the lung. We hypothesized that non-toxic analogs of IPO could be competitive inhibitors of the metabolic activation of NNK. We had shown previously that 4-hydroxy-1-phenyl-1-pentanone (HPP) and 7-hydroxy-1-phenyl-1-octanone (4-HPO) are effectively inhibiting the lung tumor activity of NNK in A/J mice. In these extended studies we have synthesized 11 new analogs of HPP and tested them for their in vitro activities as inhibitors of the metabolism of NNK. The present study demonstrated that the lipophilicity in the molecule is playing an important role for the inhibition of NNK metabolism with pulmonary and hepatic microsomes of A/J mice.

引用

页码：155 / 162

页数：8

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