Cladosins L-O, new hybrid polyketides from the endophytic fungus Cladosporium sphaerospermum WBS017

Feng Pan; Dina H El-Kashef; Rainer Kalscheuer; Werner E G Müller; Jungho Lee; Michael Feldbrügge; Attila Mándi; Tibor Kurtán; Zhen Liu; Wei Wu; Peter Proksch

doi:10.1016/j.ejmech.2020.112159

Cladosins L-O, new hybrid polyketides from the endophytic fungus Cladosporium sphaerospermum WBS017

Eur J Med Chem. 2020 Apr 1:191:112159. doi: 10.1016/j.ejmech.2020.112159. Epub 2020 Feb 19.

Authors

Feng Pan¹, Dina H El-Kashef², Rainer Kalscheuer³, Werner E G Müller⁴, Jungho Lee⁵, Michael Feldbrügge⁵, Attila Mándi⁶, Tibor Kurtán⁶, Zhen Liu⁷, Wei Wu⁸, Peter Proksch⁹

Affiliations

¹ Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine-Universität Düsseldorf, 40225, Düsseldorf, Germany; Department of Production of Special Utilized Plant, Agronomy College, Sichuan Agricultural University, No. 211, Huimin Rd, Wenjiang Region, Chengdu, 611130, Sichuan, PR China; Guizhou Provincial College-based Key Lab for Tumor Prevention and Treatment with Distinctive Medicines, Research Center for Medicine & Biology, Zunyi Medical University, Zunyi, 563000, Guizhou, PR China.
² Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine-Universität Düsseldorf, 40225, Düsseldorf, Germany; Department of Pharmacognosy, Faculty of Pharmacy, Minia University, 61519, Minia, Egypt.
³ Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine-Universität Düsseldorf, 40225, Düsseldorf, Germany.
⁴ Institute of Physiological Chemistry, Universitätsmedizin der Johannes Gutenberg Universität Mainz, 55128, Mainz, Germany.
⁵ Institute for Microbiology, Cluster of Excellence on Plant Sciences (CEPLAS), Bioeconomy Science Center (BioSC), Heinrich-Heine-Universität Düsseldorf, 40204, Düsseldorf, Germany; Bioeconomy Science Center (BioSC), c/o Forschungszentrum Jülich, 52425, Jülich, Germany.
⁶ Department of Organic Chemistry, University of Debrecen, P. O. Box 400, H-4002, Debrecen, Hungary.
⁷ Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine-Universität Düsseldorf, 40225, Düsseldorf, Germany. Electronic address: zhenfeizi0@sina.com.
⁸ Department of Production of Special Utilized Plant, Agronomy College, Sichuan Agricultural University, No. 211, Huimin Rd, Wenjiang Region, Chengdu, 611130, Sichuan, PR China. Electronic address: ewuwei@sicau.edu.cn.
⁹ Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine-Universität Düsseldorf, 40225, Düsseldorf, Germany. Electronic address: proksch@uni-duesseldorf.de.

PMID: 32101782
DOI: 10.1016/j.ejmech.2020.112159

Abstract

The endophytic fungus Cladosporium sphaerospermum WBS017 was obtained from healthy bulbs of Fritillaria unibracteata var. wabuensis. Fermentation of C. sphaerospermum on solid rice medium yielded three new hybrid polyketides, cladosins L-N (1-3), and a known derivative cladodionen (4). Further cultivation of this fungus on white bean medium afforded an additional new hybrid polyketide, cladosin O (5) along with three known analogues (6-8). The structures of the new compounds were elucidated using a combination of NMR and HRESIMS data. The absolute configurations of compounds 2 and 3 were determined by Mosher's method and TDDFT-ECD calculations. All isolated compounds were evaluated for their cytotoxic and antimicrobial activities. Cladodionen (4) exhibited cytotoxicity against the mouse lymphoma cell line L5178Y with an IC₅₀ value of 3.7 μM, and also exhibited antifungal activity against Ustilago maydis and Saccharomyces cerevisiae, while cladosin L (1) displayed week antibacterial activity against Staphylococcus aureus ATCC 29213 and S. aureus ATCC 700699 with MIC values of 50 and 25 μM, respectively.

Keywords: Antimicrobial activities; Cladosporium sphaerospermum; Cytotoxicity; Electronic circular dichroism; Hybrid polyketide.

MeSH terms

Acinetobacter baumannii / drug effects
Animals
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / isolation & purification
Anti-Bacterial Agents / pharmacology*
Antifungal Agents / chemistry
Antifungal Agents / isolation & purification
Antifungal Agents / pharmacology*
Antineoplastic Agents / chemistry
Antineoplastic Agents / isolation & purification
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Cladosporium / chemistry*
Density Functional Theory
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Enterococcus faecalis / drug effects
Mice
Microbial Sensitivity Tests
Molecular Structure
Mycobacterium tuberculosis / drug effects
Polyketides / chemistry
Polyketides / isolation & purification
Polyketides / pharmacology*
Pseudomonas aeruginosa / drug effects
Saccharomyces cerevisiae / drug effects
Staphylococcus aureus / drug effects
Structure-Activity Relationship
Ustilago / drug effects

Substances

Anti-Bacterial Agents
Antifungal Agents
Antineoplastic Agents
Polyketides