2. Academic Validation
  3. Structure-yeast α-glucosidase inhibitory activity relationship of 9-O-berberrubine carboxylates

Structure-yeast α-glucosidase inhibitory activity relationship of 9-O-berberrubine carboxylates

  • Sci Rep. 2023 Nov 1;13(1):18865. doi: 10.1038/s41598-023-45116-0.
Duy Vu Nguyen 1,  Kowit Hengphasatporn 2,  Ade Danova 1 3,  Aphinya Suroengrit 4,  Siwaporn Boonyasuppayakorn 4,  Ryo Fujiki 2,  Yasuteru Shigeta 2,  Thanyada Rungrotmongkol 5 6,  Warinthorn Chavasiri 7
Affiliations

Affiliations

  • 1 Department of Chemistry, Faculty of Science, Center of Excellence in Natural Products Chemistry, Chulalongkorn University, Pathumwan, Bangkok, 10330, Thailand.
  • 2 Center for Computational Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan.
  • 3 Organic Chemistry Division, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Bandung, West Java, 40132, Indonesia.
  • 4 Department of Microbiology, Faculty of Medicine, Center of Excellence in Applied Medical Virology, Chulalongkorn University, Bangkok, 10330, Thailand.
  • 5 Bioinformatics and Computational Biology Program, Graduated School, Chulalongkorn University, Bangkok, 10330, Thailand.
  • 6 Department of Biochemistry, Faculty of Science, Center of Excellence in Biocatalyst and Sustainable Biotechnology, Chulalongkorn University, Bangkok, 10330, Thailand.
  • 7 Department of Chemistry, Faculty of Science, Center of Excellence in Natural Products Chemistry, Chulalongkorn University, Pathumwan, Bangkok, 10330, Thailand. warinthorn.c@chula.ac.th.
PMID: 37914757 DOI: 10.1038/s41598-023-45116-0
Abstract

Thirty-five 9-O-berberrubine carboxylate derivatives were synthesized and evaluated for yeast α-glucosidase inhibitory activity. All compounds demonstrated better inhibitory activities than the parent compounds berberine (BBR) and berberrubine (BBRB), and a positive control, acarbose. The structure-activity correlation study indicated that most of the substituents on the benzoate moiety such as methoxy, hydroxy, methylenedioxy, benzyloxy, halogen, trifluoromethyl, nitro and alkyl can contribute to the activities except multi-methoxy, fluoro and cyano. In addition, replacing benzoate with naphthoate, cinnamate, piperate or diphenylacetate also led to an increase in inhibitory activities except with phenyl acetate. 9, 26, 27, 28 and 33 exhibited the most potent α-glucosidase inhibitory activities with the IC50 values in the range of 1.61-2.67 μM. Kinetic study revealed that 9, 26, 28 and 33 interacted with the Enzyme via competitive mode. These four compounds were also proved to be not cytotoxic at their IC50 values. The competitive inhibition mechanism of these four compounds against yeast α-glucosidase was investigated using molecular docking and molecular dynamics simulations. The binding free energy calculations suggest that 26 exhibited the strongest binding affinity, and its binding stability is supported by hydrophobic interactions with D68, F157, F158 and F177. Therefore, 9, 26, 28 and 33 would be promising candidates for further studies of antidiabetic activity.

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