15658-20-5Relevant academic research and scientific papers
EMETINE DERIVATIVES, PRODRUGS CONTAINING SAME, AND METHODS OF TREATING CONDITIONS USING SAME
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Page/Page column 24-25, (2012/12/13)
Compounds are provided herein which are emetine derivatives that can be used as prodrugs which selectively undergo activation to release emetine in specific cellular conditions. In one aspect, a blocking group is incorporated onto the emetine molecule by the derivization of the N2'-position with moieties that can be selectively removed by hydrolysis in the cancer/tumor microenvironment. Such compounds are less cytotoxic than emetine and are substantially inactive in non-cancerous cells. In one aspect, the compounds described herein can be used for the treatment of metastatic and non-metastatic cancers, including, for example, breast cancer, prostate cancer, lung cancer, and leukemia.
Design, synthesis, and evaluation of pH-dependent hydrolyzable emetine analogues as treatment for prostate cancer
Akinboye, Emmanuel S.,Rosen, Marc D.,Denmeade, Samuel R.,Kwabi-Addo, Bernard,Bakare, Oladapo
, p. 7450 - 7459 (2012/10/29)
The N-2′ position of the natural product emetine has been derivatized to thiourea, urea, sulfonamide, dithiocarbamate, carbamate, and pH responsive hydrolyzable amide analogues. In vitro studies of these analogues in PC3 and LNCaP prostate cancer cell lines showed that the analogues are generally less cytotoxic (average IC50 ranging from 0.079 to 10 μM) than emetine (IC50 ranging from 0.0237 to 0.0329 μM). The pH sensitive sodium dithiocarbamate salt 13 and the amide analogues 21, 22, 26 (obtained from maleic and citraconic anhydrides) showed the most promise as acid-activatable prodrugs under mildly acidic conditions found in the cancer microenvironment. These prodrugs released 12-83% of emetine at pH 6.5 and 41-95% emetine at pH 5.5. Compounds 13 and 26 were further shown to exhibit increased cytotoxicity in PC3 cell culture medium that was already below pH 7.0 at the time of treatment.
