二氢紫水晶素在阻断4-（甲基亚硝基氨基）-1-（3-吡啶基）-1-丁酮诱导的A/J小鼠O-甲基鸟嘌呤和肺癌中的体内构效关系初步研究
Pilot in Vivo Structure-Activity Relationship of Dihydromethysticin in Blocking 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone-Induced O-Methylguanine and Lung Tumor in A/J Mice.
作者信息
Puppala Manohar, Narayanapillai Sreekanth C, Leitzman Pablo, Sun Haifeng, Upadhyaya Pramod, O'Sullivan M Gerard, Hecht Stephen S, Xing Chengguo
机构信息
Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota , Minneapolis, Minnesota 55455, United States.
Department of Medicinal Chemistry, College of Pharmacy, University of Florida , Gainesville, Florida 32610, United States.
出版信息
J Med Chem. 2017 Sep 28;60(18):7935-7940. doi: 10.1021/acs.jmedchem.7b00921. Epub 2017 Sep 13.
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 O-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.
摘要
（+）-二氢紫铆因最近被确定为一种有前景的肺癌化学预防剂，而（+）-二氢卡瓦因则完全无效。研究了一个初步的体内构效关系（SAR），评估了其类似物在阻断4-（甲基亚硝基氨基）-1-（3-吡啶基）-1-丁酮诱导的A/J小鼠肺组织短期O-甲基鸟嘌呤和长期腺瘤形成方面的功效。两项结果都揭示了连贯的构效关系，表明二氢紫铆因中的亚甲二氧基官能团至关重要，而内酯官能团则可耐受修饰。
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