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Novel Anthracenones and Anthraquinones from the Toxic Fruit of K. parvifolia Horacio F. Olivo, M. Yolanda Rios, Claudia Rojas, and Rebeca Lopez-Marure The toxicity of fruit of Karwinskia has been known since the Spanish came to America. The shrub known as “coyotillo” or “tullidora” grows from Southern Texas, all over Mexico, Central America, and Colombia. Ingestion of the fruit leads to paralysis of the limbs and eventually death. Several natural products, including anthracenones and dimeric anthracenones, have been isolated and characterized from the fruit and also the roots of the plant by different research groups. |
A dimeric dihydroxyanthracenone, with a molecular weight of 514, was isolated from K. humboldtiana and became the focus of several biological studies. This molecule was found to damage the lungs and liver when ingested by experimental mice at lethal concentration. Interestingly, this molecule was found to be more toxic to several cancer cell lines in lung, liver, and colon, than to normal cell lines of these tissues. Indeed, T-514 resulted cytotoxic in liver, lung, and colon cancer cell lines at sub-lethal doses. T-514 caused a decrease in the number of liver peroxisomes. Peroxisomes are organelles that contain oxidative enzymes responsible to oxidize fatty acids and generate hydrogen peroxide. They also contain peroxidases that utilize that hydrogen peroxide to oxidize other substrates, thus eliminating the dangerous hydrogen peroxide. Catalase, also found in peroxisomes, is responsible for the breakdown of hydrogen peroxide in the cell. T-514 was found to inhibit catalase in vitro, but not in vivo. Screening of different species of Karwinskia revealed that a larger amount of T-514 was found in K. parvifolia. Motivated by the large therapeutic index and the intriguing mechanism of action of T-514, we started a program on investigating the chemistry and biology of this dimeric dihydroxyanthracenone. A collection of fruit from K. parvifolia was made, and a chloroform extract was employed to carry out a chromatographic separation. Several known anthracenones were isolated, but also some new anthracenones and anthraquinones related to T-514. Cytotoxicity studies of these molecules on both cancer and normal cells are currently the focus of our research and these results will be discussed in the presentation.  |
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