title: Curcumin analogs as potent aldose reductase inhibitors.
abstract: In the present study, curcuminoids isolated from curcuma longa were demonstrated to possess inhibitory activities on bovine lens aldose reductase. In order to find more potent aldose reductase inhibitor, curcumin analogs were synthesized and evaluated for their ability to inhibit bovine lens aldose reductase enzyme. The results indicated that the compounds with tetrahydroxyl groups, 2,6-bis(3,4-dihydroxybenzylidene)cyclohexanone (A(2)), 2,5-bis(3,4-dihydroxybenzylidene)cyclopentanone (B(2)), 1,5-bis(3,4-dihydroxyphenyl)-1,4-pentadiene-3-one (C(2)), and 3,5-bis(3,4-dihydroxybenzylidene)-4-piperidone (D(2)) showed remarkably potent inhibitory effects on aldose reductase with IC(50) of 2.9 microM, 2.6 microM, 3.4 microM, and 4.9 microM, respectively. The structure-activity relationship revealed that the curcumin analogs with ortho-dihydroxyl groups could form a more tight affinity with aldose reductase to exert more potential inhibitory activities.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhi-Yun
authors.initials: ZY
authors.lastname: Du
authors.forename: Ya-Dan
authors.initials: YD
authors.lastname: Bao
authors.forename: Zhong
authors.initials: Z
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Qiao
authors.forename: Lin
authors.initials: L
authors.lastname: Ma
authors.forename: Zhi-Shu
authors.initials: ZS
authors.lastname: Huang
authors.forename: Lian-Quan
authors.initials: LQ
authors.lastname: Gu
authors.forename: Albert S C
authors.initials: AS
authors.lastname: Chan
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D002417:Cattle; D003474:Curcumin / Q000031:analogs & derivatives* / Q000302:isolation & purification; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D000449:Aldehyde Reductase; D003474:Curcumin