Synthesis and in vitro evaluation of botryllazine B analogues as a new class of inhibitor against human aldose reductase |
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Authors: | Ryota Saito Mai Tokita Chikako Ishikawa |
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Institution: | a Department of Chemistry, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan b Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan |
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Abstract: | Botryllazine B analogues of diverse substitution patterns have been prepared, and their in vitro inhibitory activities against recombinant human aldose reductase (h-ALR2) evaluated. Among the 15 compounds tested, 6-(4-aminophenyl)-2-(4-hydroxyphenyl)carbonylpyrazine (7b) proved to be the most potent inhibitor, with IC50=0.91 μM. Kinetic analyses of 7b and botryllazine B (1) revealed that these inhibitors exhibit an unprecedented mixed-type inhibition on h-ALR2 with respect to the substrate d,l-glyceraldehyde, in the presence of NADPH at inhibitor concentrations near the IC50 values. |
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Keywords: | Reductase inhibitor Pyrazine Mixed competitive/uncompetitive inhibition |
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