title: Synthesis and biological evaluation of steroidal derivatives as selective inhibitors of AKR1B10.
abstract: AKR1B10 is a member of human aldo-keto reductase superfamily, and a promising anti-cancer therapeutic target. In this paper, androst-5-ene-3β-ol, dehydroepiandrosterone, pregnenolone and cholesterol were used as reactants, sixteen products were obtained through Jones reaction and reduction reaction using NaBH4. Their inhibitory activities against AKR1B10 and AKR1B1 were measured. The most active compound (3a) has the IC50 of 0.50μM for AKR1B10, and the most AKR1B10 selective compound (2a) has the IC50 of 0.81μM with AKR1B1/AKR1B10 selectivity of 195. In addition, the binding modes of 2a and 3a in the active site of human AKR1B10 were identified by docking.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan East Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan East Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan East Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, PR China.
authors.forename: Liping
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan Road II, Guangzhou 510080, PR China.
authors.forename: Wenli
authors.initials: W
authors.lastname: Chen
authors.affiliation: Engineering School, Sun Yat-sen University, 132 Waihuan East Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, PR China.
authors.forename: Xinying
authors.initials: X
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan East Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, PR China.
authors.forename: Minyu
authors.initials: M
authors.lastname: Xie
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan Road II, Guangzhou 510080, PR China.
authors.forename: Guangmei
authors.initials: G
authors.lastname: Yan
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan East Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, PR China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Hu
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan East Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan East Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, PR China. Electronic address: zhjingx@mail.sysu.edu.cn.
authors.forename: Jingxia
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000074408:Aldo-Keto Reductases; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008968:Molecular Conformation; D013237:Stereoisomerism; D013256:Steroids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D013256:Steroids; C120471:AKR1B10 protein, human; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase
keywords: AKR1B10; Aldose reductase; Inhibitors; Molecular docking; Steroidal derivatives