Carbonic anhydrase inhibitors--Part 94. 1,3,4-thiadiazole-2-sulfonamidederivatives as antitumor agents?
Potent sulfonamide inhibitors of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), derivatives of I ,3,4-thiadiazole-2-sulfonamide, possessing inhibition constants in the range of 10(-8)-10(-9) M against isozymes II and IV, were shown to act as efficient in vitro tumour cell growth inhibitors with GI(50) (molarity of inhibitor producing a 50% inhibition of tumour cell growth) values typically in the range of 0.1-30 microM against several leukaemia, non-small cell lung cancer, ovarian, melanoma, colon, CNS, renal, prostate and breast cancer cell lines. The mechanism of antitumour action with the new sulfonamides reported here is unknown, but it might involve either inhibition of several CA isozymes (such as CA IX, CA XII, CA XIV) present predominantly in tumour cell membranes, acidification of the intracellular environment as a consequence of CA inhibition, uncoupling of mitochondria and/or strong CA V inhibition, or a combination of several such mechanisms. Such derivatives might lead to the development of effective novel types of anticancer agents/therapies. ¿ 2000 Editions scientifiques et m|dicales Elsevier SAS.
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D000970:Antineoplastic Agents / Q000494:pharmacology*; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002257:Carbonic Anhydrase Inhibitors; D013449:Sulfonamides; D002256:Carbonic Anhydrases