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dc.contributor.author Kato, Atsushi
dc.contributor.author Kobayashi, Kaori
dc.contributor.author Narukawa, Kayo
dc.contributor.author Minoshima, Yuka
dc.contributor.author Adachi, Isao
dc.contributor.author Hirono, Shuichi
dc.contributor.author Nash, Robert J.
dc.date.accessioned 2011-06-09T11:45:48Z
dc.date.available 2011-06-09T11:45:48Z
dc.date.issued 2010-10-01
dc.identifier.citation Kato , A , Kobayashi , K , Narukawa , K , Minoshima , Y , Adachi , I , Hirono , S & Nash , R J 2010 , ' 6,7-Dihydroxy-4-phenylcoumarin as inhibitor of aldose reductase 2 ' Bioorganic & Medicinal Chemistry Letters , vol 20 , no. 19 , pp. 5630-5633 . , 10.1016/j.bmcl.2010.08.038 en
dc.identifier.issn 0960-894X
dc.identifier.other PURE: 164154
dc.identifier.other dspace: 2160/7034
dc.identifier.uri http://hdl.handle.net/2160/7034
dc.description Kato, A., Kobayashi, K., Narukawa, K., Minoshima, Y., Adachi, I., Hirono, S., Nash, R. J. (2010). 6,7-Dihydroxy-4-phenylcoumarin as inhibitor of aldose reductase 2.   Bioorganic & Medicinal Chemistry Letters, 20(19), 5630-5633. IMPF: 02.66 Sponsorship: Czech Science Foundation 525/08/H060; Institutional Research Project MZE 0002701404 en
dc.description.abstract We report the structure–activity relationship of a series of coumarins as aldose reductase 2 (ALR2) inhibitors and their suppressive effect on the accumulation of galactitol in the rat lens. We evaluated their ALR2 selectivity profile against sorbitol dehydrogenase and aldehyde reductase (ALR1). Our study revealed that substitutions in the C7 OH group enhanced the potency toward ALR2, while the C6 OH group interferes with ALR1 inhibition activity. Having the phenyl moiety at C4 leads to improved potency and improved selectivity. A molecular docking study suggested that 6,7-dihydroxy-4-phenylcoumarin (15) binds to ALR2 in a different manner from epalrestat. Furthermore, compound 15 clearly suppressed galactitol accumulation in a dose-dependent manner. These results provide an insight into the structural requirements of coumarins for developing a new-type of selective ALR2 inhibitor. en
dc.format.extent 4 en
dc.language.iso eng
dc.relation.ispartof Bioorganic & Medicinal Chemistry Letters en
dc.subject aldose reductase 2 en
dc.subject 6,7-dihydroxy-4-phenylcoumarin en
dc.subject ALR2 inhibitor en
dc.subject structure-activity relationships en
dc.subject molecular docking stody en
dc.subject galacitol accumulation en
dc.title 6,7-Dihydroxy-4-phenylcoumarin as inhibitor of aldose reductase 2 en
dc.type Text en
dc.type.publicationtype Article (Journal) en
dc.identifier.doi http://dx.doi.org/10.1016/j.bmcl.2010.08.038
dc.contributor.institution Aberystwyth University en
dc.contributor.institution Institute of Biological, Environmental and Rural Sciences en
dc.description.status Peer reviewed en


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