(+)-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.
Bibliographical noteFunding Information:
This work was funded by grants from National Institutes of Health: Grant R01-CA193278 (C.X.) and in part by the National Cancer Institute Cancer Center Support Grant CA 077598 (Turesky). We thank Dr. Peter Villalta of the Masonic Cancer Center’s Analytical Biochemistry shared resource for direction on the use of LC−MS/MS instrument.
© 2017 American Chemical Society.