Kobayashi, Kaoru published the artcileCytotoxic effects of benzbromarone and its 1′-hydroxy metabolite in human hepatocarcinoma FLC4 cells cultured on micro-space cell culture plates, Formula: C13H8Cl2O4S, the main research area is benzbromarone hydroxybenzbromarone CYP3A protein glutathione hepatocellular carcinoma anticancer.
Treatment with benzbromarone (BBR), a potent uricosuric drug, can be associated with liver injury. Recently, we reported that culture of human hepatocellular carcinoma FLC-4 cells on micro-space cell culture plates could increase the functional expression of drug-metabolizing enzymes including CYP3A4 and CYP2C9, which are involved in 1′-hydroxylation and 6-hydroxylation of BBR, resp. Therefore, we examined whether BBR and its two metabolites (1′-hydroxy BBR and 6-hydroxy BBR) have cytotoxic effects in FLC4 cells cultured on micro-space cell culture plates. The present study showed that BBR and 1′-hydroxy BBR, but not 6-hydroxy BBR, have cytotoxic effects in cells cultured on micro-space cell culture plates. BBR-induced cytotoxicity was decreased by CYP3A inhibitors (itraconazole and ketoconazole), an Nrf2 activator (tert-butylhydroquinone) and a GSH precursor (N-acetyl-L-cystein). In contrast, BBR-induced cytotoxicity was increased by a GSH biosynthesis inhibitor (buthionine sulfoximine) and an inhibitor of NAD(P)H quinone oxidoreductase 1 (dicoumarol). These results suggested that metabolic activation of 1′-hydroxy BBR via CYP3A, formation of quinone metabolites and the decrease in GSH levels were involved in the BBR-induced cytotoxicity observed in FLC4 cells cultured on micro-space cell culture plates.
Drug Metabolism and Pharmacokinetics published new progress about Antitumor agents. 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, Formula: C13H8Cl2O4S.
Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem