New ambuic acid derivatives from the solid culture of Pestalotiopsis neglecta and their nitric oxide inhibitory activity.

Qiu-Yue Qi,Hong-Wei Liu,Yun-Fei Pei,Feng Zhao,Er-Wei Li,Jun-Jie Han,Ke Ma,Ying Huang,Li Bao

doi:10.1038/srep09958

Abstract

Four new ambuic acid derivatives (1–4), and four known derivatives (5–8), were isolated from the solid culture of a plant pathogenic fungus Pestalotiopsis neglecta. Their structures were elucidated by extensive NMR experiments. The absolute configuration of the C-16 secondary alcohol in 1 was deduced via the CD data of the in situ formed [Rh2(OCOCF3)4] complex with the acetonide derivative of 1. The absolute configuration in 3 was assigned by comparison of the experimental and simulated electronic circular dichroism (ECD) spectrum. The NMR data of compound 5 was reported for the first time. In the nitric oxide (NO) inhibition assay, compounds 4, 6 and 7 showed inhibitory activity against the NO production in the lipopolysaccharide (LPS)-induced macrophage with IC50 values of 88.66, 11.20, and 20.80 µM, respectively.

Highlights

New ambuic acid derivatives from the solid culture of Pestalotiopsis neglecta and their nitric oxide inhibitory activity
Overproduction of nitric oxide (NO) is proved to be closely related with many pathogenic diseases, such as inflammation and cancer[3]
The anticancer drug taxol has been reported from the culture of several species of Pestalotiopsis, which provides an alternative way for the production of this valuable drug[11,12]

Summary

Results and Discussion

The ethyl acetate extract of the solid culture of the fungus P. neglecta was isolated by silica gel column chromatography and ODS column chromatography, and purified through reversed-phase high performance liquid chromatography (HPLC) to give eight ambuic acid derivatives (1–8). Analysis of its NMR data (Table 1) revealed that 3 possess the similar structural feature to ambuic acid (7), except that the carbonyl group at C-10 in 7 was replaced by an oxygenated methine in 3 Such variation was confirmed by HMBC cross peaks from H-10 to C-4, C-5, C-6, C-8, C-9, and C-11 (Figure 2). Analysis of its NMR data (Table 2) revealed that 4 possess the similar structure to 1, except that C-10 ketone in 1 was reduced to a hydroxyl, the C-16 hydroxyl group was replaced by the hydrogen, and the C-18 hydroxy was acetylated These observations were supported by HMBC crosspeaks from H-10 to C-4, C-5, C-8, C-9, H3-17 to C-15, C-16, and from H2-18, H3-21 to C-20 (Figure 2). The in vivo anti-inflammation assay and action mechanism deserve further investigation

Methods

NO inhibitory Activitya

Antifungal assay

Author contributions

Additional information