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Overcoming the Rapid Metabolism of the Promising Anticancer Natural Product Rooperol
Author(s) -
Jemal Mauricio A,
Schwartz Zachary T,
Zhao Zhenze,
Rodebaugh Mary,
Christy Quinn M,
Shelton Spencer,
Du Liqin,
Kerwin Sean M
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.634.5
Subject(s) - catechol , hela , natural product , cytotoxicity , chemistry , biochemistry , in vitro , in vivo , cancer cell , metabolism , linker , cancer , stereochemistry , pharmacology , biology , microbiology and biotechnology , genetics , computer science , operating system
Rooperol [1,5‐bis(3′,4′‐dihydroxyphenyl)pent‐1‐en‐4‐yne] is a naturally occurring bis‐catechol that was originally isolated from the African Potato ( Hypoxis hemerocallidea ). Rooperol shows promising anti‐cancer activity in vitro , but it is rapidly and completely metabolized to inactive phase‐II metabolites in vivo . To address this problem, analogues of rooperol have been designed in which the linker separating the catechol groups is varied or in which some or all of the catechol groups are replaced with more metabolically stable isosteres in order to explore the role of the bis‐catechol groups and the effect of catechol replacement on anticancer activity. Here we report the synthesis and cancer cell cytotoxicity of these rooperol analogs. Based upon the activity of these compounds in a cell growth inhibition assay with HeLa cells, we conclude that the bis‐catechol nature of rooperol is not an essential feature for its cytotoxicity and that an analog of rooperol that is predicted to be more resistant to metabolism yet which retains much of the anti‐cancer activity of the natural product can be identified. Support or Funding Information William and Ella Owens Medical Research Foundation and Texas State University This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .