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A manganese-salen complex as dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes

Zhu, Ming-rong, Zhou, Jie, Jin, Yi, Gao, Li-Hui, Li, Ling, Yang, Jun-Ru, Lu, Chun-Mei, Zhao, Qi Hua, Xie, Ming-jin
International journal of biological macromolecules 2018 v.120 pp. 1232-1239
X-ray diffraction, active sites, acute toxicity, blood glucose, dipeptidyl-peptidase IV, glycemic effect, in vivo studies, inhibitory concentration 50, manganese, mice, molecular models, noninsulin-dependent diabetes mellitus, schiff bases
A manganese Schiff base complex with N,N′-1,2-phenylenediamine-bis(salicyladimine) was synthesized and characterized by X-ray crystallography. This complex was administered intragastrically to alloxan-diabetic mice 3 weeks. In vivo tests showed that the complex significantly lowered serum glucose levels in alloxan-diabetic mice at doses of 77 mg V kg−1. Meanwhile, this complex was investigated as dipeptidyl peptidase IV (DPP-IV) inhibitor for the treatment of type 2 diabetes. The compound exhibit moderate inhibition against DPP-IV and possessed an IC50 value of 30 μM. Lineweaver–Burk transformation of the inhibition kinetics data demonstrated that it was a noncompetitive inhibitor of DPP-IV and Ki value was 136.3 μM. Moreover, molecular modeling studies suggested that the complex could fit well within the active-site cleft of DPP-IV. An acute toxicity study showed that animals treated intragastically with complex 1 at a dose of 5.0 g/kg did not show any significantly abnormal signs. These preliminary results suggest that the manganese Schiff base complex can induce a hypoglycemic effect in alloxan-diabetic mice.