2. Academic Validation
  3. Polyketides from the marine-derived fungus Aspergillus falconensis: In silico and in vitro cytotoxicity studies

Polyketides from the marine-derived fungus Aspergillus falconensis: In silico and in vitro cytotoxicity studies

  • Bioorg Med Chem. 2021 Jan 1:29:115883. doi: 10.1016/j.bmc.2020.115883.
Dina H El-Kashef 1,  Fadia S Youssef 2,  Irene Reimche 3,  Nicole Teusch 3,  Werner E G Müller 4,  Wenhan Lin 5,  Marian Frank 6,  Zhen Liu 6,  Peter Proksch 7
Affiliations

Affiliations

  • 1 Institute of Pharmaceutical Biology and Biotechnology, Faculty of Mathematics and Natural Sciences, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany; Department of Pharmacognosy, Faculty of Pharmacy, Minia University, 61519 Minia, Egypt.
  • 2 Institute of Pharmaceutical Biology and Biotechnology, Faculty of Mathematics and Natural Sciences, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany; Department of Pharmacognosy, Faculty of Pharmacy, Ain Shams University Abbassia, 11566 Cairo, Egypt.
  • 3 Department of Biomedical Sciences, Institute of Health Research and Education, University of Osnabrück, 49074 Osnabrück, Germany.
  • 4 Institute of Physiological Chemistry, Johannes Gutenberg University Mainz, 55128 Mainz, Germany.
  • 5 State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.
  • 6 Institute of Pharmaceutical Biology and Biotechnology, Faculty of Mathematics and Natural Sciences, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany.
  • 7 Institute of Pharmaceutical Biology and Biotechnology, Faculty of Mathematics and Natural Sciences, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany; Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang 443002, China.
PMID: 33248353 DOI: 10.1016/j.bmc.2020.115883
Abstract

Fermentation of the marine-derived fungus Aspergillus falconensis, isolated from sediment collected from the Red Sea, Egypt on solid rice medium containing 3.5% NaCl yielded a new dibenzoxepin derivative (1) and a new natural isocoumarin (2) along with six known compounds (3-8). Changes in the metabolic profile of the fungus were induced by replacing NaCl with 3.5% (NH4)2SO4 that resulted in the accumulation of three further known compounds (9-11), which were not detected when the fungus was cultivated in the presence of NaCl. The structures of the new compounds were elucidated by HRESIMS and 1D/2D NMR as well as by comparison with the literature. Molecular docking was conducted for all isolated compounds on crucial Enzymes involved in the formation, progression and metastasis of Cancer which included human cyclin-dependent kinase 2 (CDK-2), human DNA Topoisomerase II (TOP-2) and matrix metalloproteinase 13 (MMP-13). Diorcinol (7), sulochrin (9) and monochlorosulochrin (10) displayed notable stability within the active pocket of CDK-2 with free binding energy (ΔG) equals to -25.72, -25.03 and -25.37 Kcal/mol, respectively whereas sulochrin (9) exerted the highest fitting score within MMP-13 active center (ΔG = -33.83 Kcal/mol). In vitro cytotoxic assessment using MTT assay showed that sulochrin (9) exhibited cytotoxic activity versus L5178Y mouse lymphoma cells with an IC50 value of 5.1 µM and inhibition of migration of MDA-MB 231 breast Cancer cells at a concentration of 70 µM.

Keywords

Aspergillus falconensis; Cytotoxicity; Molecular docking; OSMAC; Polyketides.

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