Semisynthesis and antibacterial activities of nidulin derivatives

Isaka, Masahiko; Yangchum, Arunrat; Supothina, Sumalee; Veeranondha, Sukitaya; Komwijit, Somjit; Phongpaichit, Souwalak

doi:10.1038/s41429-018-0133-0

Cited by 12 publications

(10 citation statements)

References 7 publications

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“…These data indicate that A. unguis possesses a much higher potential for producing chlorinated NPs than A. terreus. The tri-chlorinated NP nidulin that was found in this study is also known from A. unguis and A. nidulans, and has been characterized to possess antibacterial and moderate antifungal activities [17,18,[64][65][66][67][68]. In co-cultural experiments G3-G6 in this study, the yield of nidulin was reduced although it remained at considerable levels of 14% to 56% of the yield from monocultures.…”

Section: Discussionsupporting

confidence: 50%

Secondary Metabolite Variation and Bioactivities of Two Marine Aspergillus Strains in Static Co-Culture Investigated by Molecular Network Analysis and Multiple Database Mining Based on LC-PDA-MS/MS

Wang

Glukhov

et al. 2022

Antibiotics

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Co-culture is known as an efficient way to explore the metabolic potential of fungal strains for new antibiotics and other therapeutic agents that could counter emerging health issues. To study the effect of co-culture on the secondary metabolites and bioactivities of two marine strains, Aspergillus terreus C23-3 and Aspergillus. unguis DLEP2008001, they were co-cultured in live or inactivated forms successively or simultaneously. The mycelial morphology and high-performance thin layer chromatography (HPTLC) including bioautography of the fermentation extracts were recorded. Furthermore, the agar cup-plate method was used to compare the antimicrobial activity of the extracts. Based on the above, liquid chromatography-photodiode array-tandem mass spectrometry (LC-PDA-MS/MS) together with Global Natural Products Social molecular networking (GNPS) and multiple natural products database mining were used to further analyze their secondary metabolite variations. The comprehensive results showed the following trends: (1) The strain first inoculated will strongly inhibit the growth and metabolism of the latter inoculated one; (2) Autoclaved A. unguis exerted a strong inducing effect on later inoculated A. terreus, while the autoclaved A. terreus showed high stability of its metabolites and still potently suppressed the growth and metabolism of A. unguis; (3) When the two strains are inoculated simultaneously, they both grow and produce metabolites; however, the A. terreus seemed to be more strongly induced by live A. unguis and this inducing effect surpassed that of the autoclaved A. unguis. Under some of the conditions, the extracts showed higher antimicrobial activity than the axenic cultures. Totally, A. unguis was negative in response but potent in stimulating its rival while A. terreus had the opposite effect. Fifteen MS detectable and/or UV active peaks showed different yields in co-cultures vs. the corresponding axenic culture. GNPS analysis assisted by multiple natural products databases mining (PubChem, Dictionary of Natural Products, NPASS, etc.) gave reasonable annotations for some of these peaks, including antimicrobial compounds such as unguisin A, lovastatin, and nidulin. However, some of the peaks were correlated with antagonistic properties and remain as possible novel compounds without mass or UV matching hits from any database. It is intriguing that the two strains both synthesize chemical ‘weapons’ for antagonism, and that these are upregulated when needed in competitive co-culture environment. At the same time, compounds not useful in this antagonistic setting are downregulated in their expression. Some of the natural products produced during antagonism are unknown chlorinated metabolites and deserve further study for their antimicrobial properties. In summary, this study disclosed the different responses of two Aspergillus strains in co-culture, revealed their metabolic variation, and displayed new opportunities for antibiotic discovery.

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Section: Discussionsupporting

confidence: 50%

Secondary Metabolite Variation and Bioactivities of Two Marine Aspergillus Strains in Static Co-Culture Investigated by Molecular Network Analysis and Multiple Database Mining Based on LC-PDA-MS/MS

Wang

Glukhov

et al. 2022

Antibiotics

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“…Nidulin, nornidulin, and unguinol were isolated from A. unguis ATCC 10032. The culture was cultivated in potato dextrose broth (PDB), including 4 g/L potato starch (Difco), and 20 g/L dextrose (Difco) supplemented with 2% NaCl (Sigma-Aldrich) as previously reported . The cultivation was carried out at 25 °C for 40 days under static conditions.…”

Section: Methodsmentioning

confidence: 99%

Fungal Depsidones Stimulate AKT-Dependent Glucose Uptake in 3T3-L1 Adipocytes

Chantarasakha,

Yangchum,

Isaka

et al. 2024

J. Nat. Prod.

Self Cite

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Enhanced glucose uptake in insulin-sensitive tissues is one of the therapeutic strategies to ameliorate hyperglycemia and maintain glucose homeostasis in type 2 diabetes. This study disclosed the role of fungal depsidones in glucose uptake and the underlying mechanism in 3T3-L1 adipocytes. Depsidones, including nidulin, nornidulin, and unguinol, isolated from Aspergillus unguis, stimulate glucose uptake in adipocytes. Compared to the others, nidulin exhibited an upward trend in glucose uptake. The effect of nidulin was found to be dose-and time-dependent. Nidulin also enhanced insulin-and metformin-stimulated glucose uptake. Upregulation of GLUT4 expression and AKT and AMPK phosphorylation were observed with nidulin treatment. Blockage of AKT, but not AMPK, phosphorylation was largely accompanied by diminished glucose uptake. In agreement, nidulin triggered the translocation of GLUT4 to the plasma membrane. Importantly, nidulin elevated glucose uptake associated with increased AKT phosphorylation in insulinresistant adipocytes. Taken together, nidulin could stimulate glucose uptake mainly through AKT-dependent GLUT4 translocation, serving as a seed compound in drug discovery for type 2 diabetes.

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“… Isaka et al (2019) synthesized derivatives of 146 utilizing regioselective arylation, acylation, and alkylation reactions to give 8-O-substituted analogs that were assessed for their antibacterial potential. Many of the 8-O-alkyl derivatives had more powerful antibacterial capacities than 146 , whereas 8-O - butyl exhibited the highest potential against B. cereus (MIC 0.391 μg/mL), however, the derivatives with long sidechains, as well as acylated derivatives displayed weaker capacity.…”

Section: Semisynthetic Depsidone Derivativesmentioning

confidence: 99%

“…Many of the 8-O-alkyl derivatives had more powerful antibacterial capacities than 146 , whereas 8-O - butyl exhibited the highest potential against B. cereus (MIC 0.391 μg/mL), however, the derivatives with long sidechains, as well as acylated derivatives displayed weaker capacity. On the other hand, O-aryl analogs demonstrated powerful antibacterial potential against MRSA ( Isaka et al, 2019 ) ( Fig. 14 ).…”

Section: Semisynthetic Depsidone Derivativesmentioning

confidence: 99%

Recent advances on natural depsidones: sources, biosynthesis, structure-activity relationship, and bioactivities

Khayat

Ghazawi

Samman

et al. 2023

PeerJ

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Depsidones are a class of polyphenolic polyketides that have been proposed to be biosynthesized from oxidative coupling of esters of two polyketidic benzoic acid derivatives. They are principally encountered in fungi and lichens. In addition to their diversified structural features, they revealed varied bioactivities such as antimicrobial, antimalarial, cytotoxic, anti-inflammatory, anti-Helicobacter pylori, antimycobacterial, antihypertensive, anti-diarrheal, antidiabetic, phytotoxic, anti-HIV, anti-osteoclastogenic, and butyrylcholinesterase, tyrosinase, hyaluronidase, and acetylcholinesterase inhibition. The current work was targeted to provide an overview on the naturally reported depsidones from various sources in the period from 2018 to the end of 2022 including their structures, biosynthesis, sources, and bioactivities, as well as the reported structure-activity relationship and semisynthetic derivatives. A total of 172 metabolites with 87 references were reviewed. The reported findings unambiguously demonstrated that these derivatives could be promising leads for therapeutic agents. However, further in-vivo evaluation of their potential biological properties and mechanistic investigations are needed.

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Semisynthesis and antibacterial activities of nidulin derivatives

Cited by 12 publications

References 7 publications

Secondary Metabolite Variation and Bioactivities of Two Marine Aspergillus Strains in Static Co-Culture Investigated by Molecular Network Analysis and Multiple Database Mining Based on LC-PDA-MS/MS

Secondary Metabolite Variation and Bioactivities of Two Marine Aspergillus Strains in Static Co-Culture Investigated by Molecular Network Analysis and Multiple Database Mining Based on LC-PDA-MS/MS

Fungal Depsidones Stimulate AKT-Dependent Glucose Uptake in 3T3-L1 Adipocytes

Recent advances on natural depsidones: sources, biosynthesis, structure-activity relationship, and bioactivities

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