Bio-guided discovery of antibacterial metabolites from Penicillium chrysogenum
Bio-guided isolation from the Red Sea-derived Penicillium chrysogenum yielded two new metabolites, 15-deoxy-15-amino-citreohybridonol (6) and chrysogenotoxin (7), alongside five known compounds: emodin (1), chrysophanol (2), bis(2-ethylhexyl) phthalate (3), haenamindole (4), and citreorosein (5). Co...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2025.2547258 |
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| author | Amira Mira Fatma M. Abdel Bar Ahmed I. Foudah Mohamed H. Aboutaleb Tarek S. Ibrahim Ahmed H.E. Hassan Ashraf T. Khalil |
| author_facet | Amira Mira Fatma M. Abdel Bar Ahmed I. Foudah Mohamed H. Aboutaleb Tarek S. Ibrahim Ahmed H.E. Hassan Ashraf T. Khalil |
| author_sort | Amira Mira |
| collection | DOAJ |
| description | Bio-guided isolation from the Red Sea-derived Penicillium chrysogenum yielded two new metabolites, 15-deoxy-15-amino-citreohybridonol (6) and chrysogenotoxin (7), alongside five known compounds: emodin (1), chrysophanol (2), bis(2-ethylhexyl) phthalate (3), haenamindole (4), and citreorosein (5). Compound 6 exhibited broad-spectrum antibacterial activity against both Gram-positive (MIC: 0.31–0.62 μM; MBC: 0.31–0.62 μM) and Gram-negative bacteria (MIC: 0.15–1.25 μM; MBC: 0.62–2.5 μM). Compound 7 showed potent bactericidal activity against Gram-negative bacteria (MIC: 0.07–0.31 μM; MBC: 0.15–0.62 μM) with MBC/MIC ≤ 4, while compound 4 selectively inhibited S. pneumoniae (MIC: 0.31 μM; MBC: 0.62 μM). Compounds 4, 6, and 7 exhibited low cytotoxicity towards human intestinal epithelial cells (HIEC-6). Molecular docking studies targeting the NDM-1 β-lactamase identified compounds 4, 6, and 7 as potential inhibitors of New Delhi metallo-β-lactamase-1 (NDM-1). Molecular dynamics simulations confirmed the structural stability of 7 within the NDM-1 active site. Chrysogenotoxin (7) was suggested as a promising antibacterial candidate against antibiotic-resistant pathogens. |
| format | Article |
| id | doaj-art-217a379e6c1e4672b2f91f0723089f5a |
| institution | Kabale University |
| issn | 1475-6366 1475-6374 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj-art-217a379e6c1e4672b2f91f0723089f5a2025-08-26T12:03:53ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742025-12-0140110.1080/14756366.2025.2547258Bio-guided discovery of antibacterial metabolites from Penicillium chrysogenumAmira Mira0Fatma M. Abdel Bar1Ahmed I. Foudah2Mohamed H. Aboutaleb3Tarek S. Ibrahim4Ahmed H.E. Hassan5Ashraf T. Khalil6Department of Pharmacognosy and Pharmaceutical Chemistry, College of Dentistry and Pharmacy, Burayda Colleges, Buraydah, Kingdom of Saudi ArabiaDepartment of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi ArabiaDepartment of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi ArabiaPharmaceutical Chemistry Department, Faculty of Pharmacy, Horus University, Damietta, EgyptDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, EgyptDepartment of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura, EgyptBio-guided isolation from the Red Sea-derived Penicillium chrysogenum yielded two new metabolites, 15-deoxy-15-amino-citreohybridonol (6) and chrysogenotoxin (7), alongside five known compounds: emodin (1), chrysophanol (2), bis(2-ethylhexyl) phthalate (3), haenamindole (4), and citreorosein (5). Compound 6 exhibited broad-spectrum antibacterial activity against both Gram-positive (MIC: 0.31–0.62 μM; MBC: 0.31–0.62 μM) and Gram-negative bacteria (MIC: 0.15–1.25 μM; MBC: 0.62–2.5 μM). Compound 7 showed potent bactericidal activity against Gram-negative bacteria (MIC: 0.07–0.31 μM; MBC: 0.15–0.62 μM) with MBC/MIC ≤ 4, while compound 4 selectively inhibited S. pneumoniae (MIC: 0.31 μM; MBC: 0.62 μM). Compounds 4, 6, and 7 exhibited low cytotoxicity towards human intestinal epithelial cells (HIEC-6). Molecular docking studies targeting the NDM-1 β-lactamase identified compounds 4, 6, and 7 as potential inhibitors of New Delhi metallo-β-lactamase-1 (NDM-1). Molecular dynamics simulations confirmed the structural stability of 7 within the NDM-1 active site. Chrysogenotoxin (7) was suggested as a promising antibacterial candidate against antibiotic-resistant pathogens.https://www.tandfonline.com/doi/10.1080/14756366.2025.2547258Penicillium chrysogenummarine fungiantibacterial agentsβ-lactamase inhibitionantibiotic resistance |
| spellingShingle | Amira Mira Fatma M. Abdel Bar Ahmed I. Foudah Mohamed H. Aboutaleb Tarek S. Ibrahim Ahmed H.E. Hassan Ashraf T. Khalil Bio-guided discovery of antibacterial metabolites from Penicillium chrysogenum Journal of Enzyme Inhibition and Medicinal Chemistry Penicillium chrysogenum marine fungi antibacterial agents β-lactamase inhibition antibiotic resistance |
| title | Bio-guided discovery of antibacterial metabolites from Penicillium chrysogenum |
| title_full | Bio-guided discovery of antibacterial metabolites from Penicillium chrysogenum |
| title_fullStr | Bio-guided discovery of antibacterial metabolites from Penicillium chrysogenum |
| title_full_unstemmed | Bio-guided discovery of antibacterial metabolites from Penicillium chrysogenum |
| title_short | Bio-guided discovery of antibacterial metabolites from Penicillium chrysogenum |
| title_sort | bio guided discovery of antibacterial metabolites from penicillium chrysogenum |
| topic | Penicillium chrysogenum marine fungi antibacterial agents β-lactamase inhibition antibiotic resistance |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2025.2547258 |
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