Bio-guided discovery of antibacterial metabolites from Penicillium chrysogenum.

IF 5.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-08-26 DOI:10.1080/14756366.2025.2547258

Amira Mira, Fatma M Abdel Bar, Ahmed I Foudah, Mohamed H Aboutaleb, Tarek S Ibrahim, Ahmed H E Hassan, Ashraf T Khalil

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引用次数: 0

Abstract

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.

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生物引导下发现青霉菌的抗菌代谢物。

从红海衍生的青霉菌中生物引导分离得到两种新的代谢物，15-脱氧-15-氨基-柠檬酸杂交醇(6)和黄毒素(7)，以及五种已知化合物：大黄素(1)，大黄酚(2)，双（2-乙基己基）邻苯二甲酸酯(3),haenaminole(4)和citreorosein(5)。化合物6对革兰氏阳性菌（MIC: 0.31 ~ 0.62 μM; MBC: 0.31 ~ 0.62 μM）和革兰氏阴性菌（MIC: 0.15 ~ 1.25 μM; MBC: 0.62 ~ 2.5 μM）均具有广谱抗菌活性。化合物7对革兰氏阴性菌（MIC: 0.07 ~ 0.31 μM, MBC: 0.15 ~ 0.62 μM）具有较强的抑菌活性，且MBC/MIC≤4；化合物4对肺炎链球菌（MIC: 0.31 μM, MBC: 0.62 μM）具有选择性抑制作用。化合物4、6和7对人肠上皮细胞（HIEC-6）具有低细胞毒性。针对NDM-1 β-内酰胺酶的分子对接研究发现，化合物4、6和7是新德里金属-β-内酰胺酶-1 （NDM-1）的潜在抑制剂。分子动力学模拟证实了NDM-1活性位点内7的结构稳定性。黄基因毒素(7)被认为是一种有希望的抗抗生素耐药病原体的候选抗菌药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Enzyme Inhibition and Medicinal Chemistry 医学-生化与分子生物学

CiteScore

10.30

自引率

10.70%

发文量

195

审稿时长

4-8 weeks

期刊介绍： Journal of Enzyme Inhibition and Medicinal Chemistry publishes open access research on enzyme inhibitors, inhibitory processes, and agonist/antagonist receptor interactions in the development of medicinal and anti-cancer agents. Journal of Enzyme Inhibition and Medicinal Chemistry aims to provide an international and interdisciplinary platform for the latest findings in enzyme inhibition research. The journal’s focus includes current developments in: Enzymology; Cell biology; Chemical biology; Microbiology; Physiology; Pharmacology leading to drug design; Molecular recognition processes; Distribution and metabolism of biologically active compounds.