Anticancer activity profiling of parthenolide analogs generated via P450-mediated chemoenzymatic synthesis.

ABSTRACT: The plant-derived sesquiterpene lactone parthenolide (PTL) was recently found to possess promising anticancer activity but elaboration of this natural product scaffold for optimization of its pharmacological properties has proven challenging via available chemical methods. In this work, P450-catalyzed C-H hydroxylation of positions C9 and C14 in PTL was coupled to carbamoylation chemistry to yield a panel of novel carbamate-based PTL analogs ('parthenologs'). These compounds, along with a series of other C9- and C14-functionalized parthenologs obtained via O-H acylation, alkylation, and metal-catalyzed carbene insertion, were profiled for their cytotoxicity against a diverse panel of human cancer cell lines. These studies led to the discovery of several parthenologs with significantly impr

SUBMITTER: Alwaseem H 

PROVIDER: S-EPMC5803483 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature