Sporulaminals A (1) and B (2), a pair of unusual epimeric spiroaminal derivatives, bearing a 6/4/5/5 tetracyclic ring system derived from bergamotane sesquiterpenoid, were isolated from a marine-derived fungus Paraconiothyrium sporulosum YK-03. Their structures including the absolute configurations were elucidated by extensive NMR experiments, crystal X-ray diffraction and computational electronic circular dichroism (ECD) method. Furthermore, the epimerization induced by pH, temperature and H2O was revealed, together with the hypothetical biosynthetic pathway.
Methicillin-resistant Staphylococcus aureus (MRSA), a WHO high-priority pathogen that can cause great harm to living beings, is a primary cause of death from antibiotic-resistant infections. In the present study, six new compounds, including fumindoline A–C (1–3), 12β, 13β-hydroxy-asperfumigatin (4), 2-epi-tryptoquivaline F (17) and penibenzophenone E (37), and thirty-nine known ones were isolated from the marine-derived fungus Aspergillus fumigatus H22. The structures and the absolute configurations of the new compounds were unambiguously assigned by spectroscopic data, mass spectrometry (MS), electronic circular dichroism (ECD) spectroscopic analyses, quantum NMR and ECD calculations, and chemical derivatizations. Bioactivity screening indicated that nearly half of the compounds exhibit antibacterial activity, especially compounds 8 and 1 1, and 33–38 showed excellent antimicrobial activities against MRSA, with minimum inhibitory concentration (MIC) values ranging from 1.25 to 2.5 μM. In addition, compound 8 showed moderate inhibitory activity against Mycobacterium bovis (MIC: 25 μM), compound 10 showed moderate inhibitory activity against Candida albicans (MIC: 50 μM), and compound 13 showed strong inhibitory activity against the hatching of a Caenorhabditis elegans egg (IC50: 2.5 μM).
Background: The progression of liver disease causes metabolic transformation in vivo and thus affects corresponding endogenous small molecular compounds. Metabonomics is a powerful technology which is able to assess global low-molecular-weight endogenous metabolites in a biological system. This review is intended to provide an overview of a metabonomics approach to the drug toxicology of diseases of the liver. Methods: The regulation of, and relationship between, endogenous metabolites and diseases of the liver is discussed in detail. Furthermore, the metabolic pathways involved in drug interventions of liver diseases are reviewed. Evaluation of the protective mechanisms of traditional Chinese medicine in liver diseases using metabonomics is also reviewed. Examples of applications of metabolite profiling concerning biomarker discovery are highlighted. In addition, new developments and future prospects are described. Results: Metabonomics can measure changes in metabolism relating to different stages of liver disease, so metabolic differences can provide a basis for the diagnosis, treatment and prognosis of various diseases. Conclusion: Metabonomics has great advantages in all aspects of the therapy of liver diseases, with good prospects for clinical application.