Pilot in Vivo Structure-Activity Relationship of Dihydromethysticin in Blocking 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone-Induced O6-Methylguanine and Lung Tumor in A/J Mice

(+)-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-pyrid...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2017-09, Vol.60 (18), p.7935-7940
Main Authors: Puppala, Manohar, Narayanapillai, Sreekanth C, Leitzman, Pablo, Sun, Haifeng, Upadhyaya, Pramod, O'Sullivan, M Gerard, Hecht, Stephen S, Xing, Chengguo
Format: Article
Language:English
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Summary:(+)-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.
ISSN:0022-2623
1520-4804
DOI:10.1021/acs.jmedchem.7b00921