Aspergillines E−L with TDPs inhibitory and combined anti-tumor activities from marine fungus Aspergillus sp. EGF 15-0-3 as environmental-induced products

Abstract

Systematical screening of the metabolic profile of marine fungus Aspergillus sp. EGF 15-0-3 using OSMAC-GNPS molecular networking cascade followed by target isolation of the environmental-induced products resulted the identification of eight unprecedented indole diketopiperazine-based hybrids (1−8) featuring three distinct chemical backbones. The structures of the obtained compounds were established by combination of extensive spectroscopic analyses, X-ray crystallography, and ECD calculations. All these environmental-induced metabolites were demonstrated to be unusual tyrosyl-DNA phosphodiesterase 2 inhibitors. Compound 3, as the most outstanding example, showed selective synergistic antitumor effect when combined with the chemotherapeutic drugs.

Keywords

Environmental-induced products / TDPs inhibitory activities / Combined anti-tumor activities / Marine fungus / Aspergillus sp. EGF 15-0-3

Funding

Acknowledgment

This paper is dedicated to Profs. Longnei Zeng and Jingyu Su (School of Chemistry and Chemical Engineering, Sun Yat-Sen University) on the occasion of their 96^th birthday.

Declaration of competing interest

These authors have no conflict of interest to declare.

Supplementary data

Supplementary data for this study can be obtained by contacting the corresponding authors via E-mail.

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