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

Int J Biol Macromol

School of Chemical Science and Technology, Yunnan University, Kunming 650091, Yunnan, China. Electronic address:

Published: December 2018

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. 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 IC 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.

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http://dx.doi.org/10.1016/j.ijbiomac.2018.08.089DOI Listing

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