Novel Antimicrobial Compounds as Ophiobolin-Type Sesterterpenes and Pimarane-Type Diterpene From Bipolaris Species TJ403-B1.

Six previously undescribed ophiobolin-type sesterterpenes, namely, bipolatoxins A-F (1-6); and one previously undescribed pimarane-type diterpene, namely, 1ß-hydroxy momilactone A (7); together with three known compounds, namely, 25-hydroxyophiobolin I (8), ophiobolin I (9), and ophiobolin A lactone (10); were isolated and identified from the endophytic fungus Bipolaris species TJ403-B1. Their structures with absolute configurations were elucidated on the basis of extensive spectroscopic analyses (including 1D and 2D nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectroscopy data), single-crystal X-ray diffraction analyses, and comparison of experimental circular dichroism data. All compounds (except for 5) were evaluated for antimicrobial potential, which indicated that bipolatoxin D (4) showed significant inhibitory activity against Enterococcus faecalis with a minimum inhibitory concentration (MIC) value of 8 µg/mL, and ophiobolin A lactone (10) showed significant inhibitory activity against Acinetobacter baumannii and E. faecalis with MIC values of 8 and 8 µg/mL, respectively.

Bipolaricins A-I, Ophiobolin-Type Tetracyclic Sesterterpenes from a Phytopathogenic Bipolaris sp. Fungus.

A preliminary phytochemical investigation on the EtOAc extracts of the fungus Bipolaris sp. TJ403-B1 resulted in the identification of 12 ophiobolin-type phytotoxins (1-12), including nine new ones, termed bipolaricins A-I (1-9). The structures of 1-9 were elucidated via spectroscopic data (including HRESIMS and 1D and 2D NMR) and single-crystal X-ray diffraction (Cu Kα) analyses. All of the isolated compounds were tested in terms of HMG-CoA reductase inhibitory, anti-inflammatory, and cytotoxic activities. Compound 10 showed HMG-CoA reductase inhibitory activity (IC50 = 8.4 ± 0.4 µM), and 2, 3, and 10-12 showed significant inhibitory potency against lipopolysaccharide (LPS)-induced nitric oxide production, with IC50 values in the range of 5.1 ± 0.3 to 20 ± 1 µM. Further experiments showed that 10 could significantly inhibit the production of IL-1ß, RANTES, MIP-1ß, and TNF-α as well as enhance the release of IL-13 in macrophages through the inhibition of HO-1 induction as well as the NF-κB pathway. These findings provide a scientific rationale for an anti-inflammatory therapeutic and a template for a new HMG-CoA reductase inhibitor to produce a potential anti-hyperlipidemia agent.

Amiaspochalasins A-H, Undescribed Aspochalasins with a C-21 Ester Carbonyl from Aspergillus micronesiensis.

Amiaspochalasins A-H (1-8), eight undescribed aspochalasins, and trichalasin D (9), a known analogue, were isolated from the solid culture of Aspergillus micronesiensis. Compounds 1-9 are aspochalasins with a C-21 ester carbonyl, and their structures were determined by spectroscopic data, X-ray crystallographic analyses, electronic circular dichroism calculations, and chemical methods. The CH3-25 in compound 1 is located at C-16 rather than C-14 in the previously reported aspochalasins, endowing 1 with an unexpected carbon skeleton. Compounds 2 and 3 are the first examples of aspochalasins with an unprecedented 5/6/6/8 tetracyclic ring system. Compounds 4 and 5 are diastereomers of aspochalasins I and J, respectively. Compounds 6 and 7 are the first aspochalasins featuring a long open-chain system, and their absolute configurations were discussed by comparing the NMR data of the hydrolysis and methyl esterification products of 4 and 5. Compound 8 is an isomeride of 9. The cytotoxic and antimicrobial effects of 1-9 were tested.