JOURNAL OF CHEMICAL RESEARCH
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2024
·
IF 1
Wuzhang Liu,Yu Shan,Songtao Liu,Ye Zhou,Yan Wang,Linwei Li,Shu Xu,Yu Chen,Xu Feng,Li Lin,Jinyue Luo,Fei Liu
Tachysterol is an intermediate product in the synthesis of vitamin D2 from ergosterol and vitamin D3 from 7-dehydrocholesterol under ultraviolet irradiation. Recent studies have shown that tachysterol is also a crucial intermediate in the synthesis of the natural anti-tumor product Chaxine C. Although there have been numerous studies on the synthesis of vitamin D2 and other photoisomers from ergosterol, research on the synthesis of tachysterol is relatively limited. In addition, the yield of tachysterol is not high (57.0%), and the mechanism is unclear. In this study, a method was developed for the qualitative and quantitative analysis of tachysterol. Meanwhile, an efficient synthesis process for tachysterol was reported. The qualitative and quantitative analysis of ergosterol isomers, including tachysterol, a precursor of vitamin D2, and photosterol, was conducted using high-performance liquid chromatography, and the quantitative method for tachysterol was confirmed using quantitative nuclear magnetic resonance. There were strong linear relationships between tachysterol content and the testing parameters, with the correlation coefficients of 0.9997 and 0.9971, respectively. The synthesis process of tachysterol from ergosterol through our self-designed photoreactors was optimized, and the effects of reaction temperature, reaction time, photoprotectants, reaction substrate concentration, and the power of ultraviolet lamps were investigated. The yield of the reaction was 85.7%, which is 28.7% higher than the previously reported results. The mechanism and by-products of the reaction were further studied using ultraviolet spectrophotometry and gas chromatography mass spectrometry. This study explored the potential for the large-scale preparation of tachysterol, particularly for the total synthesis of the anti-tumor natural product Chaxine C. It also offered insights into the synthesis of structural similar compounds and the analysis of photocatalytic reaction products.
研究领域:
生物化学
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药物合成
·
光化学
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Journal of Fungi
·
2021
·Vol. 7
·期 6
·432
·
IF 5.816
Qiuli OuYang,Yangmei Liu,Okwong Reymick Oketch,Miaoling Zhang,Xingfeng Shao,Nengguo Tao
Ergosterol (ERG) is a potential target for the development of antifungal agents againstPenicillium digitatum, the pathogen of green mold in citrus fruits. This study examined the mechanism by which citronellal, a typical terpenoid ofCymbopogon nardusessential oil, acts on ergosterol to exhibit its antifungal activity againstP. digitatum. We previously reported that citronellal inhibited the growth ofP. digitatumwith minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of 1.36 and 2.72 mg/mL, respectively. In citronellal-treated cells, the membrane integrity and ergosterol contents significantly decreased, whereas lanosterol, which serves as a precursor for ergosterol biosynthesis, massively accumulated. Addition of 150 mg/L of exogenous ergosterol decreased the inhibitory rate of citronellal, restoring the ergosterol content and hence the membrane structure to normal levels, and triggered expression of nearly all ERG genes. Based on our findings, we deduce that citronellal damages the cell membrane integrity ofP. digitatumby down-regulating the ERG genes responsible for conversion of lanosterol to ergosterol, the key downregulated gene beingERG3, due to the observed accumulation of ergosta-7,22-dienol.Keywords:citrus;pathogen;ergosterol;ERG genes;cell membrane integrity
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Journal of Fungi
·
2023
·Vol. 9
·期 2
·237
·
IF 4.7
Feifei Wu,Heqin Wang,Qiufeng Chen,Xiao Pang,Hao Jing,Lijun Yin,Xiuqing Zhang
It has been demonstrated that lignin was efficiently degraded byLentinula edodes(L. edodes). However, the process of lignin degradation and utilization byL. edodeshas not been discussed in detail. Therefore, the effects of lignin onL. edodesmycelium growth, chemical compositions, and phenolic profiles were investigated herein. It has been revealed that 0.10% lignin acted as the most effective concentration to accelerate mycelia growth, which yielded the highest biomass of 5.32 ± 0.07 g/L. Furthermore, a 0.10% concentration of lignin promoted the accumulation of phenolic compounds, especially protocatechuic acid, with peak value of 48.5 ± 1.2 μg/g. In contrast, the higher concentration of lignin (0.20%) exerted an inhibitory effect on the growth ofL. edodes. Overall, the application of lignin at the optimal concentration of 0.10% could not only enhance the mycelial growth but also accumulate the phenolic acids and raise the nutritional and medical values ofL. edodes.Keywords:lignin;shiitake mushroom;biomass;phenolic compound
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2019
·
IF 3.571
Xiangmin Song,Xinyue Zhu,Ting Li,Cai Liang,Meng Zhang,Yu Shao,Jun Tao,Ranfeng Sun
A series of dehydrozingerone derivatives were synthesized, and their fungicidal activities and action mechanism against Colletotrichum musae were evaluated. The bioassay result showed that most compounds exhibited excellent fungicidal activity in vitro at 50 μg mL–1. Compounds 13, 16, 18, 19, and 27 exhibited broad-spectrum fungicidal activity; especially, compounds 19 and 27 were found to have more potent fungicidal activity than azoxystrobin. The EC50 values of compounds 19 and 27 against Rhizoctonia solani were 0.943 and 0.161 μg mL–1 respectively. Moreover, compound 27 exhibited significant in vitro bactericidal activity against Xanthomonas oryzae pv. oryzae, with an EC50 value of 11.386 μg mL–1, and its curative effect (49.64%) and protection effect (51.74%) on rice bacterial blight disease was equivalent to that of zhongshengmycin (42.90%, 40.80% respectively). Compound 27 could also effectively control gray mold (87.10%, 200 μg mL–1) and rice sheath blight (100%, 200 μg mL–1; 82.89%, 100 μg mL–1) in vivo. Preliminary action mechanism study showed that compound 27 mainly acted on the cell membrane and significantly inhibited ergosterol biosynthesis in Colletotrichum musae.
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DEVELOPMENTAL CELL
·
2024
·
IF 10.7
Rongrong He,Ziwei Lv,Yinan Li,Shuchao Ren,Jiaqi Cao,Jun Zhu,Xinrong Zhang,Huimin Wu,Lihao Wan,Ji Tang,Shutong Xu,Xiao-Lin Chen,Zhipeng Zhou
Ergosterols are essential components of fungal plasma membranes. Inhibitors targeting ergosterol biosynthesis (ERG) genes are critical for controlling fungal pathogens, including Magnaporthe oryzae , the fungus that causes rice blast. However, the translational mechanisms governing ERG gene expression remain largely unexplored. Here, we show that the Trm6/Trm61 complex catalyzes dynamic N 1 -methyladenosine at position 58 (m 1 A58) in 51 transfer RNAs (tRNAs) of M. oryzae , significantly influencing translation at both the initiation and elongation stages. Notably, tRNA m 1 A58 promotes elongation speed at most cognate codons mainly by enhancing eEF1-tRNA binding rather than affecting tRNA abundance or charging. The absence of m 1 A58 leads to substantial decreases in the translation of ERG genes, ergosterol production, and, consequently, fungal virulence. Simultaneously targeting the Trm6/Trm61 complex and the ergosterol biosynthesis pathway markedly improves rice blast control. Our findings demonstrate an important role of m 1 A58-mediated translational regulation in ergosterol production and fungal infection, offering a potential strategy for fungicide development.
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MOLECULAR BIOLOGY REPORTS
·
2012
·Vol. 39
·期 10
·9493-9508
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IF 2.929
Cheng Zhengjun
This study was designed to examine the interactions of ergosterol with bovine serum albumin (BSA) and human serum albumin (HSA) under physiological conditions with the drug concentrations in the range of 2.99–105.88 μM and the concentration of proteins was fixed at 5.0 μM. The analysis of emission spectra quenching at different temperatures revealed that the quenching mechanism of HSA/BSA by ergosterol was the static quenching. The number of binding sites n and the binding constants K were obtained at various temperatures. The distance r between ergosterol and HSA/BSA was evaluated according to Föster non-radioactive energy transfer theory. The results of synchronous fluorescence, 3D fluorescence, FT-IR, CD and UV–Vis absorption spectra showed that the conformations of HSA/BSA altered in the presence of ergosterol. The thermodynamic parameters, free energy change (Δ G ), enthalpy change (Δ H ) and entropy change (Δ S ) for BSA–ergosterol and HSA–ergosterol systems were calculated by the van’t Hoff equation and discussed. Besides, with the aid of three site markers (for example, phenylbutazone, ibuprofen and digitoxin), we have reported that ergosterol primarily binds to the tryptophan residues of BSA/HSA within site I (subdomain II A).
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY
·
2025
·Vol. 95
·期 4
·902-913
·
IF 0.8
Luo R.,Hou L. M.,Wang Q.,Lin Y.,Deng S. Q.,Wang L.,Bu M.
Combining antitumor drugs with fluorescent groups to form therapeutic prodrugs has important application value in cancer treatment. In this study, we designed and synthesized a novel anticancer therapeutic prodrug, 2-(benzo[ d ]thiazol-2-yl)-4-methoxyphenyl 4-{[4-(ergosterol peroxide-3-yl-oxy)-4-oxobutyl]disulfaneyl}butanoate. The synthesis was achieved by covalently linking ergosterol peroxide (EP) and 2-(benzo[ d ]thiazol-2-yl)-4-methoxyphenol through a disulfide (S–S) bond. The reaction of the prodrug with high-concentration GSH in tumor tissues broke the disulfide bond, dissociating it into free EP and activated fluorescent BTMP, enabling the visual monitoring of the drug. A series of spectral analyses showed that 2-(benzo[ d ]thiazol-2-yl)-4-methoxyphenyl 4-{[4-(ergosterol peroxide-3-yl-oxy)-4-oxobutyl]disulfaneyl}butanoate could be specifically activated by high-concentration GSH and had good stability. Cytotoxicity assays showed that it had strong inhibitory activity against breast cancer MCF-7 cells but low toxicity toward human normal breast cells (MCF-10A). In addition, it could induce apoptosis and enable visual tracking in MCF-7 cells. Consequently, the specific drug-release behavior of 2-(benzo[ d ]thiazol-2-yl)-4-methoxyphenyl 4-{[4-(ergosterol peroxide-3-yl-oxy)-4-oxobutyl]disulfaneyl}butanoate within tumors renders it a highly promising prodrug candidate. This approach thus offers a viable strategy for tumor diagnosis and treatment.
研究领域:
药理学
·
肿瘤学
·
化学合成
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Virulence
·
2026
·
IF 6.8
Ya-Hong Wang,Die Zhu,Dan Wang,Ruo-Cheng Sheng,Li-Chao Wang,Chen-Ning Zhang,Muhammad Faizan Latif,Huan Li,Feng-Mao Chen
The normal polar growth and morphogenesis represent fundamental factors in development, reproduction survival and host invasion of phytopathogenic fungi. The heterotetramerized AP-2 complex is widely present in eukaryotes and plays a specific role in clathrin-mediated vesicle formation and transport at the plasma membrane in mammals and plants. However, the functions of AP-2 complex in growth, metabolism and virulence of plant pathogenic fungi remain unclear. In this study, the conserved VdAP-2α subunit was identified in Verticillium dahliae by screening of a T-DNA insertion library. VdAP-2α was significantly induced during the developmental phases of V. dahliae, and its GFP-fused signals exhibited a punctate distribution in cytoplasm and on the plasma membrane. Like the insertional mutant, the deletion of VdAP-2α caused the suppression of radial growth, conidiation and virulence, as well as aggravated formation of melanized microsclerotia. Comparative transcriptomic analysis further elucidated the global regulation of VdAP-2α, including hyphal growth, vesicle transport, redox reactions and metabolic processes. Moreover, the impairment of hyphal polarity disordered chitin distribution, bidirectional conidia germination and hydrophobicity, which were associated with membrane defects caused by the decreasing of membrane-associated ergosterols and intermediates. These results contribute to the understanding of the functional characteristics of the AP-2 complex in filamentous fungi and suggest potential antifungal targets.
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AAPS PHARMSCITECH
·
2020
·Vol. 21
·期 2
·1-11
·
IF 2.401
Dong Zhonghua,Iqbal Sajid,Zhao Zhongxi
In our previously studies, we confirmed that ergosterol could ameliorate diabetic nephropathy by suppressing the proliferation of mesangial cells and the accumulation of extracellular matrix (ECM). However, the therapeutic application of ergosterol may be confined due to poor aqueous solubility and low oral bioavailability. We aim to prepare ergosterol-loaded nanostructured lipid carriers (ERG-NLCs) to enhance the solubility and oral bioavailability of ergosterol. ERG-NLCs were prepared using glyceryl monostearate and decanoyl/octanoyl-glycerides by hot emulsification–ultrasonication method and characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) analysis, entrapment efficiency (EE), and drug loading (DL) capacity studies. The prepared ERG-NLCs were spherical, with particle size of 81.39 nm and negative zeta potential of 30.77 mV. Ergosterol was successfully encapsulated in NLCs with a high EE of 92.95% and a DL capacity of 6.51%. In pharmacokinetic study, C max and AUC 0-∞ of ergosterol in ERG-NLCs were obviously enhanced, and the relative oral bioavailability of ERG-NLCs was 277.56% higher than that of raw ergosterol. Moreover, the in vitro pharmacodynamic study indicated that ERG-NLCs inhibited high-glucose-stimulated mesangial cells over proliferation and ECM accumulation more effectively compared to raw ergosterol. In conclusion, the validated ERG-NLCs showed that NLCs mediated delivery could be used as potential vehicle to enhance solubility, oral bioavailability and therapeutic efficacy of ergosterol.
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MOLECULAR PLANT-MICROBE INTERACTIONS
·
2021
·
IF 4.171
Xingtao Bao,Rui Yang,Shilong Jiang,Jinping Zhao,Delu Wang,Dongxue Li,Xian Wu,Baoan Song,Zhuo Chen
Diseases caused by fungi can affect the quality and yield of the leaves of tea [ Camellia sinensis (L.) Kuntze]. At present, the availability of highly effective and safe fungicides for controlling tea plants remains limited. The objectives of this study were to identify novel compounds with antifungal activities and to determine their molecular mechanisms. A series of sulfone compounds containing 1,3,4-oxadiazole were evaluated in China for their antifungal activities against several pathogens causing foliar diseases and high production losses. Transcriptomics and bioinformatics were used to analyze the differentially expressed genes of Lasiodiplodia theobromae treated with a representative compound, jiahuangxianjunzuo (JHXJZ). Moreover, the effects of JHXJZ on ergosterol content, membrane permeability, cell structure, and seven key genes involved in the ergosterol biosynthetic pathway were investigated. JHXJZ had a strong antifungal activity against L. theobromae in vitro, with an effective concentration giving 50% inhibition of 3.54 ± 0.55 μg/ml, and its curative efficacies on detached tea leaves reached 41.78% at 100 μg/ml. JHXJZ upregulated 899 genes ( P < 0.05) and downregulated 1,185 genes ( P < 0.05) in L. theobromae . These genes were found to be associated with carbohydrate metabolic processes, which are closely related to steroid biosynthesis in the Kyoto Encyclopedia of Genes and Genomes pathways. Because JHXJZ regulates the key genes of sterol biosynthesis, it decreased the ergosterol content, increased cell-membrane permeability, changed the cellular structure, enhanced the roughness of the surface of the hyphae, and resulted in degradation of the hyphal nuclei and necrosis of the hyphal cytoplasm. Our study demonstrates that JHXJZ is a fungicide with a novel mechanism of action that differs from that of triazole fungicides. JHXJZ has potential for applications in controlling tea plant diseases.
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Food & Function
·
2025
·
IF 5.4
Zhonghua Dong,Xiao Li,Xuan Wang,Jingya Xu,Wei Xu
Background: Diabetic kidney disease (DKD), one of the most common microvascular complications of diabetes mellitus, has been considered the leading cause of end-stage renal disease. Ergosterol is a natural sterol abundant in edible fungi that exhibits pharmacological properties beneficial in the treatment of DKD. However, the precise mechanisms remain elusive. This study aimed to evaluate the therapeutic efficacy of ergosterol in DKD and to delineate the underlying mechanisms. Methods: Transcriptome microarray sequencing data from DKD patients retrieved from the public GEO database, as well as data from mouse DKD models, were analyzed to identify differentially expressed genes. Db/db mouse, high-glucose-induced HK-2 cells and conditioned THP-1 cells were employed to evaluate the impact of ergosterol on renal function, lipid metabolism and macrophage phenotypic transformation. Results: Transcriptional profiling of DKD kidneys revealed alterations in fatty acid metabolism, which were corroborated in db/db mice. Ergosterol significantly improved renal function, reduced lipid accumulation, and mitigated inflammation. CPT1A, a key modulator of fatty acid metabolism, was identified as a target. The inhibition of CPT1A in renal tubular epithelial cells led to impaired fatty acid oxidation and lipid accumulation. Excessive renal lipids further stimulated macrophages to transform into pro-inflammatory phenotypes, leading to renal inflammation infiltration and exacerbating kidney damage. Ergosterol upregulated CPT1A expression through transcriptional regulation of FOXA1, thereby reducing lipid accumulation and subsequent renal inflammation. Conclusion: Ergosterol enhances renal fatty acid oxidation via the FOXA1/CPT1A pathway, reducing renal lipid accumulation and inflammation, potentially delaying DKD progression. This study elucidates the therapeutic potential of ergosterol in DKD and provides new insights into the treatment of DKD.
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Cell Reports
·
2025
·
IF 6.9
Zu-Guo Zheng,Yi-Ping Zhang,Xiao-Yu Zhang,Meng-Yao Qin,Yin-Yue Xu,He Wu,Run-Qing Liu,Qiu-Yi Wu,Ming-Su Wang,Chong Zhang,Yue-Qin Zheng,Jian-Ye Dai,Ping Li,Hua Yang
Sterols target sterol-sensing domain (SSD) proteins to lower cholesterol and circulating and hepatic triglyceride levels, but the mechanism remains unclear. In this study, we identify acyl-coenzyme A (CoA) synthetase long-chain family member 1 (ACSL1) as a direct target of ergosterol (ES). The C-terminal domain of ACSL1 undergoes conformational changes from closed to open, and ES may target the drug-binding pocket in the acetyl-CoA synthetase-like domain 1 (ASLD1) of ACSL1 to stabilize the closed conformation and maintain its activity. Moreover, ES is mainly enriched in the mitochondria and promotes fatty acid β-oxidation through ACSL1 allosteric activation. Structure-activity relationship analysis reveals how different structural sterols interact with the sterol-sensing domain-containing protein (SCAP) and ACSL1, explaining their regulatory effects on lipid metabolism. Moreover, our findings reveal that the combination of SCAP inhibitor 25-hydroxycholesterol (25-HC) and ES has a stronger lipid-lowering effect than alone.
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