Abstract
(+)-Dihydromethysticin was recently identified as a promising lung cancer chemopreventive agent, while (+)-dihydrokavain was completely ineffective. A pilot in vivo structure-activity relationship (SAR) was explored, evaluating the efficacy of its analogs in blocking 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced short-term O6-methylguanine and long-term adenoma formation in the lung tissues in A/J mice. Both results revealed cohesive SARs, demonstrating that the methylenedioxy functional group in DHM is essential while the lactone functional group tolerates modifications.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adenoma / metabolism
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Adenoma / pathology
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Adenoma / prevention & control*
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Animals
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Anticarcinogenic Agents / chemistry
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Anticarcinogenic Agents / therapeutic use*
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Carcinogens
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Female
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Guanine / analogs & derivatives*
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Guanine / antagonists & inhibitors
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Guanine / metabolism
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Lung / drug effects*
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Lung / metabolism
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Lung / pathology
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Lung Neoplasms / chemically induced
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Lung Neoplasms / metabolism
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Lung Neoplasms / pathology
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Lung Neoplasms / prevention & control*
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Mice
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Nitrosamines
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Pyrones / chemistry
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Pyrones / therapeutic use*
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Structure-Activity Relationship
Substances
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7,8-dihydromethysticin
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Anticarcinogenic Agents
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Carcinogens
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Nitrosamines
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Pyrones
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Guanine
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4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone
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O-(6)-methylguanine