Synthesis of novel curcumin analogues for inhibition of 11β-hydroxysteroid dehydrogenase type 1 with anti-diabetic properties

• We synthesized analogues of curcumin which were much more stable than the curcumin.
• We found 4 curcumin analogues are selective inhibitors of human and rat 11β-HSD1.
• Analogues of curcumin display anti-diabetic properties.

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).

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