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

Manohar Puppala; Sreekanth C. Narayanapillai; Pablo Leitzman; Haifeng Sun; Pramod Upadhyaya; M. Gerard O'Sullivan; Stephen S. Hecht; Chengguo Xing

doi:10.1021/acs.jmedchem.7b00921

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

Manohar Puppala, Sreekanth C. Narayanapillai, Pablo Leitzman, Haifeng Sun, Pramod Upadhyaya, M. Gerard O'Sullivan, Stephen S. Hecht, Chengguo Xing

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

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.

Original language	English (US)
Pages (from-to)	7935-7940
Number of pages	6
Journal	Journal of medicinal chemistry
Volume	60
Issue number	18
DOIs	https://doi.org/10.1021/acs.jmedchem.7b00921
State	Published - Sep 28 2017

Bibliographical note

Funding 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.

Publisher Copyright:
© 2017 American Chemical Society.

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Publisher link

10.1021/acs.jmedchem.7b00921

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5729742

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Puppala, M., Narayanapillai, S. C., Leitzman, P., Sun, H., Upadhyaya, P., O'Sullivan, M. G., Hecht, S. S., & Xing, C. (2017). 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. Journal of medicinal chemistry, 60(18), 7935-7940. https://doi.org/10.1021/acs.jmedchem.7b00921

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. / Puppala, Manohar; Narayanapillai, Sreekanth C.; Leitzman, Pablo et al.
In: Journal of medicinal chemistry, Vol. 60, No. 18, 28.09.2017, p. 7935-7940.

Research output: Contribution to journal › Article › peer-review

Puppala, M, Narayanapillai, SC, Leitzman, P, Sun, H, Upadhyaya, P, O'Sullivan, MG, Hecht, SS & Xing, C 2017, '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', Journal of medicinal chemistry, vol. 60, no. 18, pp. 7935-7940. https://doi.org/10.1021/acs.jmedchem.7b00921

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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.",

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note = "Funding 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{\textquoteright}s Analytical Biochemistry shared resource for direction on the use of LC−MS/MS instrument. Publisher Copyright: {\textcopyright} 2017 American Chemical Society.",

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