Polyketides from the marine-derived fungus Aspergillus falconensis: In silico and in vitro cytotoxicity studies.
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.
['El-Kashef|Dina H|DH|', 'Youssef|Fadia S|FS|', 'Reimche|Irene|I|', 'Teusch|Nicole|N|', 'Müller|Werner E G|WEG|', 'Lin|Wenhan|W|', 'Frank|Marian|M|', 'Liu|Zhen|Z|', 'Proksch|Peter|P|']
D000818:Animals D000970:Antineoplastic Agents D001230:Aspergillus D045744:Cell Line, Tumor D002465:Cell Movement D049109:Cell Proliferation D002470:Cell Survival D004305:Dose-Response Relationship, Drug D004353:Drug Evaluation, Preclinical D004354:Drug Screening Assays, Antitumor D006801:Humans D051379:Mice D062105:Molecular Docking Simulation D015394:Molecular Structure D061848:Optical Imaging D061065:Polyketides D013329:Structure-Activity Relationship
Polyketides Aspergillus falconensis Cytotoxicity Molecular docking OSMAC