Bioprocessing of monomethyl ether from Alternaria alternata, a multi-target antiproliferative compound as emphasized by in silico analysis.

Authors

Suhaila R Alsaid, Manar M Abdel Gwad, Gamal Abdel-Fattah, Mohamed A Marawan, Yehia Osman, Samar A Khashana, Ashraf S A El-Sayed

Published in

Scientific reports. Volume 16. Issue 1. Jul 09, 2026. Epub Jul 09, 2026.

Abstract

The emergence of drug-resistant cancer cells driven by mutations, proteins tertiary structure alterations, and overexpression of drug efflux pumps, particularly P-glycoprotein (P-gp) system is the major challenge of cancer chemotherapy. Consequently, the search for affordable, stable, and multi-targeted lead compounds has become a critical objective. Alternariol monomethyl ether (AME) is known for its cytotoxic activity; nevertheless, its bioavailability and in vivo efficacy remains equivocal, which limits its further therapeutic application. Alternaria alternata LSR PV576354.1, inhabiting stored barely seeds, was isolated with the highest yields of AOH and AME as quantified by HPLC. Upon nutritional bioprocessing, the yield of AOH and AME by A. alternata was increased to 8.65 µg/ml and 10.05 µg/ml, respectively, at C:N ratio 14.2:1, of pH 5.0 after 18 days. The purified AME of A. alternata was chemically resolved from the HPLC, LC-MS and MS/MS analyses, with 272.2 m/z, and consistent fragmentation pattern of authentic AME. The maximum antiproliferative activity of AME was reported for HCT-116 (0.61 μg/ml), HepG-2 (1.72 μg/ml), MCF-7 cells (2.41 μg/ml), with selectivity indices 17.1, 6.4, 4.3 folds, compared to normal OEC cells. AME of A. alternata had a strong anti-tubulin polymerizing activity (IC₅₀ value 3.9 μg/ml), anti- topoisomerase I (IC₅₀ value 40.9 μg/ml) and II (IC₅₀ value 35.6 μg/ml) activities. The AME of A. alternata strongly induces the total, early apoptosis, late apoptosis and necrosis of the HCT-116 cells by 6.7, 19.5, 17.2 and 1.8 folds, compared to the control cells. From the molecular docking analysis, the AME of A. alternata had a conceivable binding energies with topoisomerase I, II and β-tubulin (-7.0-7.3 kcal/mol), with RMSD values 1.5 and 1.9Å, respectively. Consequently, from the experimental and in silico analyses, A. alternata AME could be a promising multi-target antiproliferative lead compound, and with further structure-activity relationship, transcriptomics and proteomics analyses, this compound could be a novel platform of cancer chemotherapy.

PMID:
42426079
Bibliographic data and abstract were imported from PubMed on 10 Jul 2026.

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