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Discovery and preliminary SAR of bisbenzylisoquinoline alkaloids as inducers of C/EBP?.

ABSTRACT: A high throughput in vitro screen has been developed to identify substances that induce expression of C/EBP? in tumor cells. An extract of the fruit of Gyrocarpus jacquinii showed induction of C/EBP? activity that was attributed to the bisbenzylisoquinoline (BBIQ) alkaloid pheanthine (13) by dereplication analysis. The research project was broadened to assess the effect of other natural BBIQ structural types occurring outside the genus Gyrocarpus. Several of the 28 compounds assayed showed enhancement of C/EBP? induction in U937 cells. The results of this study should encourage future efforts toward obtaining and screening a larger set of both natural and synthetic analogs of this interesting group of alkaloids.

SUBMITTER: Klausmeyer P

PROVIDER: S-EPMC3430122 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Discovery and preliminary SAR of bisbenzylisoquinoline alkaloids as inducers of C/EBPα.

Klausmeyer Paul P McCloud Thomas G TG Scudiero Dominic A DA Currens Michael J MJ Cardellina Ii John H JH Shoemaker Robert H RH

Bioorganic & medicinal chemistry 20120616 15

A high throughput in vitro screen has been developed to identify substances that induce expression of C/EBPα in tumor cells. An extract of the fruit of Gyrocarpus jacquinii showed induction of C/EBPα activity that was attributed to the bisbenzylisoquinoline (BBIQ) alkaloid pheanthine (13) by dereplication analysis. The research project was broadened to assess the effect of other natural BBIQ structural types occurring outside the genus Gyrocarpus. Several of the 28 compounds assayed showed enhan ...[more]

PMID: 22766217

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