ABSTRACT
Two new sclerotioramines (1 and 2) and a new natural product of sclerotioramine analog (3), together with seven known compounds have been isolated from the mangrove endophytic fungus Penicillium sclerotiorin SCNU-F0040. Their structures were identified based on the 1 D, 2 D NMR and HRESIM spectra. The absolute configurations of new compounds were deduced by specific rotation data and electronic circular dichroism spectra. All the isolated new compounds were tested on anti-diabetes activity by using a-glucosidase inhibition assay and anti-inflammatory activity by using cyclooxygenase inhibition assay, respectively. Compounds 1 and 2 have a-glucosidase inhibition activity with IC50 values of 102.3 and 217.5 µM. Compound 2 shows a moderate cyclooxygenase-2 inhibitory activity with an IC50 value of 47.8 µM.
Subject(s)
Penicillium , Penicillium/chemistry , Fungi , Glucosidases , Molecular StructureABSTRACT
Four new polyketide compounds, including two new unique isocoumarins penicillol A (1) and penicillol B (2) featuring with spiroketal rings, two new citreoviridin derivatives citreoviridin H (3) and citreoviridin I (4), along with four known analogues were isolated from the mangrove endophytic fungus Penicillium sp. BJR-P2. Their structures were elucidated by extensive spectroscopic methods. The absolute configurations of compounds 1-4 based on electronic circular dichroism (ECD) calculations, DP4+ analysis, and single-crystal X-ray diffraction are presented. All the new compounds were evaluated for anti-inflammatory activity. An anti-inflammatory assay indicated that compound 2 inhibited lipopolysaccharide (LPS)-induced NO production in RAW 264.7 cells, with half-maximal inhibitory concentration (IC50) values of 12 µM, being more potent than the positive control, indomethacin (IC50 = 35.8 ± 5.7 µM). Docking study showed that compound 2 was perfectly docking into the active site of murine inducible nitric oxide oxygenase (iNOS) via forming multiple typical hydrogen bonds.
Subject(s)
Penicillium , Polyketides , Animals , Anti-Inflammatory Agents/pharmacology , Indomethacin , Isocoumarins/chemistry , Lipopolysaccharides/pharmacology , Mice , Molecular Structure , Nitric Oxide , Oxygenases , Penicillium/chemistry , Polyketides/chemistryABSTRACT
Six new DIKETOPIPERAZINE alkaloids aspergiamides A-F (1-6), together with ten known alkaloids (7-16), were isolated from the mangrove endophytic fungus Aspergillus sp. 16-5c. The structures of the new compounds were elucidated based on 1D/2D NMR spectroscopic and HR-ESIMS data analyses. The absolute configurations of aspergiamides A-F were established based on the experimental and calculated ECD data. All the compounds were evaluated for the antidiabetic activity against α-glucosidase and PTP1B enzyme. The bioassay results disclosed compounds 1 and 9 exhibited significant α-glucosidase inhibitory with IC50 values of 18.2 and 7.6 µM, respectively; compounds 3, 10, 11, and 15 exhibited moderate α-glucosidase inhibition with IC50 values ranging from 40.7 to 83.9 µM; while no compounds showed obvious PTP1B enzyme inhibition activity.
Subject(s)
Alkaloids/pharmacology , Aspergillus/chemistry , Diketopiperazines/pharmacology , Glycoside Hydrolase Inhibitors/pharmacology , Hypoglycemic Agents/pharmacology , China , Diabetes Mellitus, Type 2 , Humans , Inhibitory Concentration 50 , WetlandsABSTRACT
The latest research has indicated that anti-tumor agents with COX-2 inhibitory activity may benefit their anti-tumor efficiency. A series of sclerotiorin derivatives have been synthesized and screened for their cytotoxic activity against human lung cancer cells A549, breast cancer cells MDA-MB-435 using the MTT method. Among them, compounds 3, 7, 12, 13, 15, 17 showed good cytotoxic activity with IC50 values of 6.39, 9.20, 9.76, 7.75, 9.08, and 8.18 µM, respectively. In addition, all compounds were tested in vitro the COX-2 inhibitory activity. The results disclosed compounds 7, 13, 25 and sclerotiorin showed moderate to good COX-2 inhibition with the inhibitory ratios of 58.7%, 51.1%, 66.1% and 56.1%, respectively. Notably, compound 3 displayed a comparable inhibition ratio (70.6%) to the positive control indomethacin (78.9%). Furthermore, molecular docking was used to rationalize the potential of the sclerotiorin derivatives as COX2 inhibitory agents by predicting their binding energy, binding modes and optimal orientation at the active site of the COX-2. Additionally, the structure-activity relationships (SARS) have been addressed.
Subject(s)
Antineoplastic Agents/pharmacology , Benzopyrans/pharmacology , Cyclooxygenase 2 Inhibitors/pharmacology , Cyclooxygenase 2/metabolism , Neoplasms/drug therapy , A549 Cells , Antineoplastic Agents/chemical synthesis , Benzopyrans/chemical synthesis , Cell Survival/drug effects , Cyclooxygenase 2 Inhibitors/chemical synthesis , Dose-Response Relationship, Drug , Humans , Inhibitory Concentration 50 , Molecular Docking Simulation , Molecular Structure , Neoplasms/pathology , Structure-Activity RelationshipABSTRACT
A pair of uncommon fused multicyclic polyketides with a two- spiro-carbon skeleton, (±)-isoepicolactone, (±)-1, and one new isobenzofuranone monomer (4), together with four other known biosynthetically related compounds were isolated from the fermentation of an endophytic fungus, Epicoccum nigrum SCNU-F0002, which was isolated from the fresh fruit of the mangrove plant Acanthus ilicifolius L. Comprehensive spectroscopic analysis, X-ray crystallography, together with calculated ECD, were employed to define the structures. The antibacterial and COX-2 inhibitory activities of the compounds (1-6) were evaluated. A possible biogenetic pathway of (±)-isoepicolactone was confirmed.
