Seven New Cytotoxic and Antimicrobial Xanthoquinodins from Jugulospora vestita.

Lulu Shao,Yasmina Marin-Felix,Marc Stadler,Frank Surup,Alberto M Stchigel

doi:10.3390/jof6040188

Abstract

During the course of a screening for novel biologically active secondary metabolites produced by the Sordariomycetes (Ascomycota, Fungi), the ex-type strain of Jugulospora vestita was found to produce seven novel xanthone-anthraquinone heterodimers, xanthoquinodin A11 (1) and xanthoquinodins B10–15 (2–7), together with the already known compound xanthoquinodin B4 (8). The structures of the xanthoquinodins were determined by analysis of the nuclear magnetic resonance (NMR) spectroscopic and mass spectrometric data. Moreover, the absolute configurations of these metabolites were established by analysis of the 1H−1H coupling constants, nuclear Overhauser effect spectroscopy (NOESY) correlations, and Electronic Circular Dichroism (ECD) spectroscopic data. Antifungal and antibacterial activities as well as cytotoxicity of all compounds were tested. Xanthoquinodin B11 showed fungicidal activities against Mucor hiemalis [minimum inhibitory concentration (MIC) 2.1 µg/mL], Rhodotorula glutinis (MIC 2.1 µg/mL), and Pichia anomala (MIC 8.3 µg/mL). All the compounds 1–8 displayed anti-Gram-positive bacteria activity (MIC 0.2–8.3 µg/mL). In addition, all these eight compounds showed cytotoxicity against KB 3.1, L929, A549, SK-OV-3, PC-3, A431, and MCF-7 mammalian cell lines. The six novel compounds (1–3, 5–7), together with xanthoquinodin B4, were also found in the screening of other strains belonging to Jugulospora rotula, revealing the potential chemotaxonomic significance of the compound class for the genus.

Highlights

Nowadays, the increasing drug resistance by bacterial and fungal pathogens and the decrease of new therapeutic agents and developmental candidates are a global hurdle [1]
Another example is the cytotoxic compounds, which can hold a great potential for the cancer treatment since these can be combined with targeted therapy, achieving the delivery of the drug to cancer cell-specific genes or proteins or to tissue microenvironment of developing cancer [4]
Based on the combined above nuclear magnetic resonance (NMR) analysis data and the molecular formula, the planar structure of 1 was elucidated as xanthone–anthraquinone heterodimer similar to xanthoquinodin A6 [21] and xanthoquinodin A9 [23]

Summary

Introduction

The increasing drug resistance by bacterial and fungal pathogens and the decrease of new therapeutic agents and developmental candidates are a global hurdle [1]. This problem has led to strong demand to increase the chemical diversity of antibiotics and antifungals, with the fungi, whose secondary metabolites remain poorly studied, being the potential solution for this challenge [2].

Methods

Results

Conclusion