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Synthesis and biological evaluation of chepraecoxin A derivatives as α-glucosidase inhibitors.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2020 Apr 15; Vol. 30 (8), pp. 127020. Date of Electronic Publication: 2020 Feb 06. - Publication Year :
- 2020
-
Abstract
- The ent-kaurane diterpenoid chepraecoxin A (CA) obtained in our previous study showed a potential inhibitory activity on α-glucosidase (IC <subscript>50</subscript> 274.5 ± 12.5 μM). In order to figure out the structure-activity relationships (SARs), twenty-two derivatives of chepraecoxin A were synthesized by modifying the ester, allyl, double bond and carboxyl groups, and assayed for their α-glucosidase inhibitory activity. Of them, eight compounds (14-17, 19-22) significantly increased activity with IC <subscript>50</subscript> values ranging from 16.1 to 71.4 μM, even higher than the positive control, acarbose (IC <subscript>50</subscript> 130.3 μM). Especially, compounds 17, 19 and 21 could inhibit α-glucosidase with IC <subscript>50</subscript> values of 16.9 ± 3.4, 16.1 ± 1.2, and 17.1 ± 0.6 μM, 17-fold higher than CA. The most active compound 19 was proven to be a non-competitive inhibitor with a K <subscript>i</subscript> value of 19.4 μM based on enzyme kinetics study. The primary SARs of CA derivatives were summarized for exploring antidiabetic candidates.<br />Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2020 Elsevier Ltd. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 30
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 32067867
- Full Text :
- https://doi.org/10.1016/j.bmcl.2020.127020