Glucuronidation, representative of II phase of metabolism, is a crucial pathway of metabolism and excretion of endogenous compounds and xenobiotics. UDP-glucuronyltransferases (UGT; EC 2.4.1.17) catalyse transformation of bilirubine, steroids and thyroid hormones, bile acids as well as exogenous compounds, including drugs, carcinogens, environmental pollutants and nutrient components. Deactivation of xenobiotics and the following excretion of hydrophilic conjugates should be a main task of glucuronidation. However, one can found glucuronides of comparable or even higher reactivity than that of the native compound. Nearly 35% of all drugs are metabolized by UGTs. Major sites of these reaction include the liver, intestine and kidney. There were found 22 functional UGT isoforms that belong to 5 subfamilies (UGT1A, 2A, 2B, 3A and 8A). Among variety of drugs conjugated by UGTs, anticancer agents are of special interest, because of the reported differences in UGT expression in normal and tumor tissues. On the other hand, glucuronidation may also represent a mechanism of intrinsic drug resistance, as it was observed for irinotecan and  metotrexat glucuronides in colon and breast cancer, respectively. It has also been shown that new types of glucuronides would play a role of prodrugs, that are hydroxylysed selectively in tumor cells. Earlier studies of our group indicated that triazolo- and imidazoacridinone antitumor agents are glucuronidated in human liver and intestine in vivo and selectively to UGT1A10 isoform in vitro. Furthermore, glucoronide of one of them gave higher cytotoxicity than parent drug. Our current results indicated that our compounds are also able to modulate enzymatic activity of UGT. Summing up, the obtained results could be exploited for the design of analogs of clinical and pharmacological importance with the aim of increasing and/or decreasing the biological response of UGT and/or eliminating any undesired side effects of glucuronidation.

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