In vitro metabolism by mouse and human liver preparations of halomon, an antitumor halogenated monoterpene

Cancer Chemotherapy and Pharmacology
M J EgorinJ L Eiseman

Abstract

To characterize the enzymes responsible for and metabolites produced from the metabolism of halomon, a halogenated monoterpene that is isolated from the red algae Portieria hornemanii and has in vitro activity in the NCI screen against brain, renal, and colon cancer cell lines. Mouse and human liver fractions, prepared by homogenization and differential centrifugation, were incubated with halomon, extracted with toluene, and analyzed by gas chromatography. In the presence of NADPH, mouse-liver 9,000-g supernatant (S9) fractions metabolized halomon, but boiled S9 fractions did not. NADH could not substitute for NADPH. Further separation of murine hepatic S9 fractions produced a microsomal fraction that contained all of the halomon-metabolizing activity; cytosol had none. Carbon monoxide reduced murine hepatic microsomal metabolism of halomon, whereas an anaerobic, N2 environment greatly accelerated the disappearance of halomon. Human hepatic microsomes metabolized halomon and required NADPH to do so. Carbon monoxide completely inhibited human hepatic microsomal metabolism of halomon. Unlike murine hepatic microsomal metabolism of halomon, anaerobic conditions did not enhance the metabolism of halomon by human hepatic microsomes....Continue Reading

Citations

Dec 14, 2011·Marine Drugs·Dioli Ann PayoOlivier de Clerck
Sep 24, 2015·Journal of the American Chemical Society·Cyril BucherNoah Z Burns
Sep 25, 2014·Chemical Communications : Chem Comm·D Christopher BraddockMariko Whyte
Oct 30, 2019·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Hongqiu ZhouYuan Wei
Aug 31, 2004·Journal of Natural Products·Sridevi AnkisettyBill J Baker
Apr 29, 2006·Journal of Natural Products·Eric H AndrianasoloWilliam H Gerwick
Nov 14, 2020·Marine Drugs·Alexander N ShikovOlga N Pozharitskaya

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