Pilot in Vivo Structure–Activity Relationship of Dihydromethysticin in Blocking 4‑(Methylnitrosamino)-1-(3-pyridyl)-1-butanone-Induced <i>O</i>⁶‑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-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.