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

6533b839fe1ef96bd12a6642

RESEARCH PRODUCT

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

Wenhan Lin Zhen Liu Nicole Teusch Fadia S. Youssef Irene Reimche Peter Proksch Werner E. G. M�ller Marian Frank Dina H. El-kashef

subject

Cell Survival Clinical Biochemistry Drug Evaluation Preclinical Pharmaceutical Science Antineoplastic Agents Biochemistry chemistry.chemical_compound Mice Structure-Activity Relationship Cell Movement Cell Line Tumor Drug Discovery Animals Humans MTT assay Cytotoxicity Molecular Biology IC50 Cell Proliferation chemistry.chemical_classification biology Dose-Response Relationship Drug Molecular Structure Topoisomerase Organic Chemistry Optical Imaging In vitro Isocoumarin Molecular Docking Simulation Enzyme Aspergillus Biochemistry chemistry Polyketides biology.protein Molecular Medicine Fermentation Drug Screening Assays Antitumor

description

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.

year	journal	country	edition	language
2020-08-17	Bioorganicmedicinal chemistry

10.1016/j.bmc.2020.115883 https://pubmed.ncbi.nlm.nih.gov/33248353