Novel Bioactive Penicipyrroether A and Pyrrospirone J from the Marine-Derived Penicillium sp. ZZ380.

Tengfei Song,Mengxuan Chen,Xiaoyuan Lian,Hengju Ge,Zhizhen Zhang,Mingmin Tang

doi:10.3390/md17050292

Abstract

The marine-sourced fungus Penicillium sp. ZZ380 was previously reported to have the ability to produce a series of new pyrrospirone alkaloids. Further investigation on this strain resulted in the isolation and identification of novel penicipyrroether A and pyrrospirone J. Each of them represents the first example of its structural type, with a unique 6/5/6/5 polycyclic fusion that is different from the 6/5/6/6 fused ring system for the reported pyrrospirones. Their structures were elucidated by extensive nuclear magnetic resonance (NMR) and high resolution electrospray ionization mass spectroscopy (HRESIMS) spectroscopic analyses, electronic circular dichroism (ECD) and 13C NMR calculations and X-ray single crystal diffraction. Penicipyrroether A showed potent antiproliferative activity against human glioma U87MG and U251 cells with half maximal inhibitory concentration (IC50) values of 1.64–5.50 μM and antibacterial inhibitory activity with minimum inhibitory concentration (MIC) values of 1.7 μg/mL against methicillin-resistant Staphylococcus aureus and 3.0 μg/mL against Escherichia coli.

Highlights

Hirsutellones and related compounds are a family of fungal secondary metabolites that bear a unique 13-membered ether ring, which is composed of the structural units of decahydrofluorene, para-cyclophane and pyrrolidinone [1,2]
An EtOAc extract prepared from a mass culture of Penicillium sp
Compound was isolated from a previous culture of ZZ380 in BMPMtomedium

Summary

Introduction

Hirsutellones and related compounds are a family of fungal secondary metabolites that bear a unique 13-membered ether ring, which is composed of the structural units of decahydrofluorene, para-cyclophane and pyrrolidinone [1,2] This family of fungal metabolites is divided into four groups: GKK1032s, hirsutellones, pyrrocidines and pyrrospirones. ZZ380 [2] was recently isolated from a wild sea crab Pachygrapsus crassipes during the course of our ongoing program to discover novel bioactive agents from marine microorganisms. This fungus in the BMPM liquid medium produced new pyrrospirones C–I (1–7) [2], penicipyrrodiether A (8) [3] and compound 10 (Figure 1), the structure of which was not possible to establish previously, due to its structural instability. Pyrrospirone G (5) was found to have potent activity against the proliferation of different glioma cells and pyrrospirones C (1), F (4), I (7) and penicipyrrodiether A (8) showed activities in inhibiting the growth of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli

Methods

Results

Conclusion