Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.108 (TAT)
 2,389 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antimalarial effects of two compounds from an aminothiol family of multidentate chelators, ethane-1,2-bis(N-1-amino-3-ethylbutyl-3-thiol) (BAT) and N',N',N'-tris(2-methyl-2-mercaptopropyl)-1,4,7-triazacyclononane (TAT), were studied in Plasmodium falciparum cultured in erythrocytes. Both drugs inhibited parasite growth, as was judged from [3H]hypoxanthine incorporation into the nucleic acids of parasites, with 50% inhibitory concentrations (IC50 values: 7.6 +/- 1.2 microM for BAT and 3.3 +/- 0.3 microM for TAT) that exceeded the antimalarial action of desferrioxamine B by 5-10 times. The inhibitory effects of both agents on P. falciparum cultures were fully reversed by pre-complexation with iron, suggesting that this action was related mainly to the withholding of iron. Spectrofluorometric studies with the fluorescent iron-sensing probe calcein showed that both compounds withheld iron from calcein at pH 8.2. The trophozoite and schizont stages of parasite development were the stages most susceptible to inhibition. The IC50 values of BAT and TAT for mammalian cells, which were estimated by [3H]thymidine incorporation into the nucleic acids of cells, were 10-20 times higher than those required to inhibit plasmodial growth. This indicates that multidentate aminothiols may prove to have a clinical margin of safety that makes them appropriate candidates for future clinical development.
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PMID:Aminothiol multidentate chelators as antimalarials. 931 71

Three compounds of an aminothiol family of iron chelators were examined for activity against trypomastigote (human) and epimastigote (vector) forms of Trypanosoma cruzi: tetraethyl and tetramethyl derivatives of ethane-1,2-bis (N-1-amino-3-ethyl butyl-3-thiol) (BAT-TE and BAT-TM) and N',N',N'-tris-(2-methyl-2-mercaptopriopyl)- 1,4,7-triazacyclonane (TAT). BAT-TE at 270 microM completely arrested the growth of trypomastigote forms in mouse blood stored at 4 degrees C for 24 h (IC(50) 67.7+/-7 microM), while BAT-TM arrested growth at 630 microM (IC(50) 158+/-17 microM) and TAT at concentrations >800 microM (IC(50) 415+/-55 microM). In T. cruzi-infected mice, BAT-TE and BAT-TM had no anti-trypanosomal activity in doses up to 200 mg/kg, whether the route of administration was intraperitoneal or oral, and TAT was not tested due to insufficient quantity. TAT had an IC(50) of 52+/-7 microM against the epimastigote forms while BAT-TM and BAT-TE were inhibitory only at concentrations >250 microM. The trypanocidal activity of BAT derivatives in blood stored at 4 degrees C makes these compounds potential candidates for the purpose of clearing donated blood of trypomastigotes.
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PMID:Aminothiol multidentate chelators against Chagas disease. 1083 86