title: Synthesis of novel curcumin analogues for inhibition of 11β-hydroxysteroid dehydrogenase type 1 with anti-diabetic properties.
abstract: In the present study, a series of mono-carbonyl analogues of curcumin were designed and synthesized by deleting the reactive beta-diketone moiety, which is responsible for the pharmacokinetic limitation of curcumin. We demonstrated that 4 of 9 curcumin analogues were selective inhibitors of human and rodent 11β-HSD1. The level of this inhibitor was 4-20 times more than that of curcumin. Curcumin analogues weakly inhibited 11β-HSD2, and further analyses revealed that these compounds were highly selective, favoring 11β-HSD1. These 4 curcumin analogues are potential therapeutic agents for type-2 diabetes by targeting 11β-HSD1. The compound 8 displays anti-diabetic properties in diabetic mice induced by streptozocin and high-fat-diet (STZHFD).
authors.affiliation: Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, PR China; Heilongjiang Key Laboratory of Tissue Damage and Repair, Mudanjiang Medical University, Heilongjiang 157011, PR China.
authors.forename: Xiaohuan
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Heilongjiang Key Laboratory of Tissue Damage and Repair, Mudanjiang Medical University, Heilongjiang 157011, PR China.
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Li
authors.affiliation: Heilongjiang Key Laboratory of Tissue Damage and Repair, Mudanjiang Medical University, Heilongjiang 157011, PR China.
authors.forename: He
authors.initials: H
authors.lastname: Bai
authors.affiliation: Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, PR China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Su
authors.affiliation: Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, PR China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xiang
authors.affiliation: Heilongjiang Key Laboratory of Tissue Damage and Repair, Mudanjiang Medical University, Heilongjiang 157011, PR China.
authors.forename: Chaonan
authors.initials: C
authors.lastname: Wang
authors.affiliation: Heilongjiang Key Laboratory of Tissue Damage and Repair, Mudanjiang Medical University, Heilongjiang 157011, PR China.
authors.forename: Binghai
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Heilongjiang Key Laboratory of Tissue Damage and Repair, Mudanjiang Medical University, Heilongjiang 157011, PR China.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, PR China.
authors.forename: Qihao
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Heilongjiang Key Laboratory of Tissue Damage and Repair, Mudanjiang Medical University, Heilongjiang 157011, PR China. Electronic address: yanhui_chu@sina.com.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Chu
authors.affiliation: Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, PR China. Electronic address: tydhuang@jnu.edu.cn.
authors.forename: Yadong
authors.initials: Y
authors.lastname: Huang
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D003474:Curcumin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced / Q000188:drug therapy*; D059305:Diet, High-Fat; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D015394:Molecular Structure; D013311:Streptozocin / Q000008:administration & dosage; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D013311:Streptozocin; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D003474:Curcumin
keywords: Anti-diabetic activity; Curcumin analogues; Pharmacokinetic; Stability