Novel Functionalized Triazole/Carbazole-Based Chitosan: In Vitro, In Vivo and In Silico Evaluation of Anti-diabetic and Anti-obesity Activities

In this work, a new triazole/carbazole based chitosan ( Cs-tri-carb ), was synthesized via the chemical modification of chitosan extracted from the exoskeleton of the pink shrimp ( Parapenaeus longirostris ) in an attempt to develop a potent antidiabetic and anti-obesity agent. The biomaterial ( Cs-tri-carb ) was elaborated by treating a previously protected chitosan azide ( Cs-N 3 ) by a propargylated carabzole ( Carb-Prop ) using Copper catalyzed regiospecific click chemistry. The structure of Cs-tri-carb was characterized using FT-IR, XPS and NMR spectroscopies. The obtained results approve the incorporation of the joined triazole/carbazole unit in the side chain of chitosan. The thermal study of Cs-tri-carb shows that the chemical modification has significantly improved its stability up to 315 °C. The biopolymer Cs-tri-carb was evaluated as an inhibitor of α-amylase and lipase activities. In vitro and in vivo studies revealed that the Cs-tri-carb exhibits a significant inhibitory action against these key enzymes. Moreover, the administration of Cs-tri-carb to surviving diabetic rats reduced the intestinal α-amylase activity by 26 and 32% and decreased the blood glucose by 26 and 40%, respectively compared to untreated diabetic rats. In addition, Chitosan or Chitosan derivative ( Cs-tri-carb ) decreased the intestinal lipase activities by 33 and 41%, and consequently, modulation of blood lipid levels as total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) rates. Overall, the findings of the current study indicate that the biomaterial Cs-tri-carb displays attractive properties and can, therefore, be considered for future application in the development of antidiabetic and hypolipidemic drugs.