Ipomeanol analogs as chemopreventive agents: effect on the in vitro metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)

Dhimant Desai, Maria Nunes, Lehua Chang, Jyh ming Lin, Ding Jiao, Shantu Amin

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)155-162
Number of pages8
JournalCancer Letters
Volume97
Issue number2
DOIs
StatePublished - Nov 6 1995

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Pentanones
Lung
Investigational Drugs
Microsomes
Carcinogens
Tobacco
4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone
In Vitro Techniques
Liver
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

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title = "Ipomeanol analogs as chemopreventive agents: effect on the in vitro metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)",
abstract = "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.",
author = "Dhimant Desai and Maria Nunes and Lehua Chang and Lin, {Jyh ming} and Ding Jiao and Shantu Amin",
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journal = "Cancer Letters",
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Ipomeanol analogs as chemopreventive agents : effect on the in vitro metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). / Desai, Dhimant; Nunes, Maria; Chang, Lehua; Lin, Jyh ming; Jiao, Ding; Amin, Shantu.

In: Cancer Letters, Vol. 97, No. 2, 06.11.1995, p. 155-162.

Research output: Contribution to journalArticle

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T2 - effect on the in vitro metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)

AU - Desai, Dhimant

AU - Nunes, Maria

AU - Chang, Lehua

AU - Lin, Jyh ming

AU - Jiao, Ding

AU - Amin, Shantu

PY - 1995/11/6

Y1 - 1995/11/6

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AB - 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.

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