Meroterpene-Like ?-Glucosidase Inhibitors Based on Biomimetic Reactions Starting from ?-Caryophyllene.

ABSTRACT: BACKGROUND:Natural meroterpenes derived from phloroglucinols and ?-caryophyllene have shown high inhibitory activity against ?-glucosidase or cancer cells, however, the chemical diversity of this type of skeletons in Nature is limited. METHODS:To expand the chemical space and explore their inhibitory activities against ?-glucosidase (EC 3.2.1.20), we employed ?-caryophyllene and some natural moieties (4-hydroxycoumarins, lawsone or syncarpic acid) to synthesize new types of meroterpene-like skeletons. All the products (including side products) were isolated and characterized by NMR, HR-MS, and ECD. RESULTS:In total, 17 products (representing seven scaffolds) were generated through a one-pot procedure. Most products (12 compounds) showed more potential activity (IC50 < 25 ?M) than the positive controls (acarbose and genistein, IC50 58.19, and 54.74 ?M, respectively). Compound 7 exhibited the most potent inhibition of ?-glucosidase (IC50 3.56 ?M) in a mixed-type manner. The CD analysis indicated that compound 7 could bind to ?-glucosidase and influence the enzyme's secondary structure. CONCLUSIONS:Compound 7 could serve as a new type of template compound to develop ?-glucosidase inhibitors. Full investigation of a biomimic reaction can be used as a concise strategy to explore diverse natural-like skeletons and search for novel lead compounds.

SUBMITTER: Yan DW 

PROVIDER: S-EPMC7024386 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature