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The assessment of antidiabetic properties of novel synthetic curcumin analogues: α-amylase and α-glucosidase as the target enzymes

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Abstract

Diabetes mellitus is a metabolic disorder characterized by high blood glucose levels and instability in carbohydrate metabolism. For treating diabetes, one important therapeutic approach is reducing the postprandial hyperglycemia which can be managed by delaying the absorption of glucose through inhibition of the carbohydrate-hydrolyzing enzymes, α-amylase (α-Amy) and α-glucosidase (α-Gls) in the digestive tract. In this work, a new class of curcumin derivatives incorporating pyrano[2,3-d]pyrimidine heterocycles was synthesized using a multicomponent reaction between curcumin, aldehydes, and barbituric acid. Using UV-Vis spectroscopic method, the synthetic compounds were assessed for their inhibitory properties against α-Amy and α-Gls enzymes. Also, the antioxidant potential of these compounds was measured spectroscopically and compared with Trolox which is known as a gold standard to measure antioxidant capacity. The results of present study suggest that the curcumin derivatives were able to efficiently inhibit both yeast and mammalian α-Gls. In comparison with the antidiabetic medicine acarbose, the synthetic curcumin derivatives were also capable to inhibit more effectively the yeast α-Gls. The partial inhibitory effects of these compounds against pancreatic α-Amy were also important in the terms of avoiding development of the possible gastrointestinal side effects. Moreover, some of the curcumin derivatives indicated stronger antioxidant activity than Trolox. Overall, these synthetic curcumin analogues might be considered as novel molecular templates for development of efficient antidiabetic compounds with promising inhibitory activities against α-Amy and α-Gls enzymes.

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Acknowledgments

The authors appreciatively acknowledge the financial support of Shiraz University and National Institute for Medical Research Development (NIMAD).

Funding

This work was supported by NIMAD (grant number 964854).

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Authors and Affiliations

  1. Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran

    Fatemeh Hasaninezhad, Zohreh Tavaf & Reza Yousefi

  2. Department of Chemistry, College of Sciences, Shiraz University, Shiraz, Iran

    Farhad Panahi, Maryam Nourisefat & Ali Khalafi-Nezhad

Authors
  1. Fatemeh Hasaninezhad
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  2. Zohreh Tavaf
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  3. Farhad Panahi
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  4. Maryam Nourisefat
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  5. Ali Khalafi-Nezhad
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  6. Reza Yousefi
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Contributions

RY, FP and AK conceived and designed research. FP and MN synthesized and characterized synthetic compounds. FH and ZT conducted biological experiments. FP and RY analyzed data and wrote the manuscript. All authors read and approved the manuscript.

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Correspondence to Farhad Panahi or Reza Yousefi.

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Hasaninezhad, F., Tavaf, Z., Panahi, F. et al. The assessment of antidiabetic properties of novel synthetic curcumin analogues: α-amylase and α-glucosidase as the target enzymes. J Diabetes Metab Disord 19, 1505–1515 (2020). https://doi.org/10.1007/s40200-020-00685-z

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