Cyclic heptapeptides from the soil-derived fungus Clonostachys rosea

Nada M Abdel-Wahab; Harwoko Harwoko; Werner E G Müller; Alexandra Hamacher; Matthias U Kassack; Mostafa A Fouad; Mohamed S Kamel; Wenhan Lin; Weaam Ebrahim; Zhen Liu; Peter Proksch

doi:10.1016/j.bmc.2019.07.025

Cyclic heptapeptides from the soil-derived fungus Clonostachys rosea

Bioorg Med Chem. 2019 Sep 1;27(17):3954-3959. doi: 10.1016/j.bmc.2019.07.025. Epub 2019 Jul 12.

Authors

Affiliations

¹ Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany; Department of Pharmacognosy, Faculty of Pharmacy, Minia University, 61519 Minia, Egypt.
² Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany; Department of Pharmacy, Faculty of Health Sciences, Universitas Jenderal Soedirman, Jalan dr. Soeparno, Karangwangkal 53123 Purwokerto, Indonesia.
³ Institute of Physiological Chemistry, Universitätsmedizin der Johannes-Gutenberg-Universität Mainz, 55128 Mainz, Germany.
⁴ Institute of Pharmaceutical and Medicinal Chemistry, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany.
⁵ Department of Pharmacognosy, Faculty of Pharmacy, Minia University, 61519 Minia, Egypt.
⁶ Department of Pharmacognosy, Faculty of Pharmacy, Minia University, 61519 Minia, Egypt; Department of Pharmacognosy, Faculty of Pharmacy, Deraya University, 61111 New Minia, Egypt.
⁷ State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.
⁸ Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany; Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address: weaamnabil@mans.edu.eg.
⁹ Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany. Electronic address: zhenfeizi0@sina.com.
¹⁰ Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany.

PMID: 31324567
DOI: 10.1016/j.bmc.2019.07.025

Abstract

Three new cyclic heptapeptides (1-3) together with three known compounds (4-6) were isolated from a solid rice culture of the soil-derived fungus Clonostachys rosea. Fermentation of the fungus on white beans instead of rice afforded a new γ-lactam (7) and a known γ-lactone (8) that were not detected in the former extracts. The structures of the new compounds were elucidated on the basis of 1D and 2D NMR spectra as well as by HRESIMS data. Compounds 1 and 4 exhibited significant cytotoxicity against the L5178Y mouse lymphoma cell line with IC₅₀ values of 4.1 and 0.1 µM, respectively. Compound 4 also displayed cytotoxicity against the A2780 human ovarian cancer cell line with an IC₅₀ value of 3.5 µM. The preliminary structure-activity relationships are discussed.

Keywords: Clonostachys rosea; Cytotoxicity; Peptides; Soil-derived fungus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / chemistry
Antineoplastic Agents / isolation & purification
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Fermentation
Gliocladium / chemistry*
Gliocladium / metabolism
Humans
Mice
Molecular Structure
Peptides, Cyclic / chemistry
Peptides, Cyclic / isolation & purification
Peptides, Cyclic / pharmacology*
Structure-Activity Relationship

Substances

Antineoplastic Agents
Peptides, Cyclic