Article
Iridoids as DNA topoisomerase I poisons
Author/s | Gálvez, Marina
Martín Cordero, Carmen Ayuso, María Jesús |
Department | Universidad de Sevilla. Departamento de Farmacología |
Publication Date | 2005 |
Deposit Date | 2022-04-08 |
Published in |
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Abstract | The discovery of new topoisomerase I inhibitors is necessary since most of the antitumor drugs are targeted against type II and
only a very few can specifically affect type I. Topoisomerase poisons generate toxic DNA ... The discovery of new topoisomerase I inhibitors is necessary since most of the antitumor drugs are targeted against type II and only a very few can specifically affect type I. Topoisomerase poisons generate toxic DNA damage by stabilization of the covalent DNA-topoisomerase cleavage complex and some have therapeutic efficacy in human cancer. Two iridoids, aucubin and geniposide, have shown antitumoral activities, but their activity against topoisomerase enzymes has not been tested. Here it was found that both compounds are able to stabilize covalent attachments of the topoisomerase I subunits to DNA at sites of DNA strand breaks, generating cleavage complexes intermediates so being active as poisons of topoisomerase I, but not topoisomerase II. This result points to DNA damage induced by topoisomerase I poisoning as one of the possible mechanisms by which these two iridoids have shown antitumoral activity, increasing interest in their possible use in cancer chemoprevention and therapy. |
Funding agencies | Ministerio de Ciencia y Tecnología (MCYT). España |
Project ID. | SAF 2000-0167 |
Citation | Gálvez, M., Martín Cordero, C. y Ayuso, M.J. (2005). Iridoids as DNA topoisomerase I poisons. Journal of Enzyme Inhibition and Medicinal Chemistry, 20 (4), 389-392. |
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