Medicinal plants have been studied for potential endophytic interactions and numerous studies have provided evidence that seeds harbor diverse microbial communities, not only on their surfaces but also within the embryo. Adenosine deaminase (ADA) is known as a potential therapeutic target for the treatment of lymphoproliferative disorders and cancer. Therefore, in this study, 20 types of medicinal plant seeds were used to screen endophytic fungi with tissue homogenate and streak. In addition, 128 morphologically distinct endophyte strains were isolated and their ADA inhibitory activity determined by a spectrophotometric assay. The strain with the highest inhibitory activity was identified as Cochliobolus sp. Seven compounds were isolated from the strain using a chromatography method. Compound 3 showed the highest ADA inhibitory activity and was identified as 5-hydroxy-2-hydroxymethyl-4H-pyran-4-one, based on the results of 1H and 13C NMR spectroscopy. The results of molecular docking suggested that compound 3 binds to the active site and the nonspecific binding site of the ADA. Furthermore, we found that compound 3 is a mixed ADA inhibitor. These results indicate that endophytic strains are a promising source of ADA inhibitors and that compound 3 may be a superior source for use in the preparation of biologically active ADA inhibitor compounds used to treat cancer.
- MeSH
- adenosindeaminasa chemie metabolismus MeSH
- Ascomycota chemie klasifikace genetika izolace a purifikace MeSH
- endofyty chemie klasifikace genetika izolace a purifikace MeSH
- inhibitory adenosindeaminasy chemie farmakologie MeSH
- léčivé rostliny mikrobiologie MeSH
- lidé MeSH
- magnetická rezonanční spektroskopie MeSH
- nádory farmakoterapie enzymologie MeSH
- semena rostlinná mikrobiologie MeSH
- simulace molekulového dockingu MeSH
- vazebná místa MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Therapeutic applications of microbial secondary metabolites provided the opportunity for the discovery of antibiotics, immunosuppressants, cholesterol lowering and anticancer drugs. Most natural products used in medicine are isolated from plants. The isolation is usually quite a difficult, expensive and non-ecological process. Therefore we focused on microbial sources of enzyme inhibitors. Although many substances were already discovered in the last century, their potential and various modifications are still promising. An interest in enzyme inhibitors is steadily growing due to their potential in the management of metabolic disorders and serious diseases and also due to finding more effective and safer drugs.
- MeSH
- alfa-amylasy antagonisté a inhibitory terapeutické užití MeSH
- alfa-glukosidasy antagonisté a inhibitory terapeutické užití MeSH
- beta-glukosidasa antagonisté a inhibitory terapeutické užití MeSH
- biologické přípravky * metabolismus terapeutické užití MeSH
- hydrolasy * antagonisté a inhibitory terapeutické užití MeSH
- inhibitory adenosindeaminasy aplikace a dávkování terapeutické užití MeSH
- inhibitory enzymů * terapeutické užití MeSH
- lidé MeSH
- mikrobiologické jevy * MeSH
- neuraminidasa antagonisté a inhibitory terapeutické užití MeSH
- proteasy MeSH
- Check Tag
- lidé MeSH
