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

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Abstract

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-N3) 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.

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Acknowledgements

The authors are grateful for the financial support of the Ministry of Higher Education and Scientific Research, Tunisia, granted to the Laboratory of Advanced Materials and Interfaces (LR-11-ES-55).

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  1. Faculty of Sciences of Monastir, Laboratory of Interfaces and Advanced Materials (LIMA), Bd. of the Environment, University of Monastir, Monastir, 5019, Tunisia

    Khaoula Hassine, Habiba Zrida, Khaled Hriz & Hatem Majdoub

  2. Faculty of Sciences of Monastir, Laboratory of Heterocyclic Chemistry, Natural Products and Reactivity (LR11ES39), Team: Medicinal Chemistry and Natural Products, Bd. of the Environment, University of Monastir, Monastir, 5019, Tunisia

    Ilyes Saidi & Hichem Ben Jannet

  3. Laboratory of Bioresources: Integrative Biology and Valorization, Higher Institute of Biotechnology of Monastir, University of Monastir, Monastir, Tunisia

    Khaled Hamdan

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Hassine, K., Zrida, H., Saidi, I. et al. Novel Functionalized Triazole/Carbazole-Based Chitosan: In Vitro, In Vivo and In Silico Evaluation of Anti-diabetic and Anti-obesity Activities. Chemistry Africa 7, 643–659 (2024). https://doi.org/10.1007/s42250-023-00790-5

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