JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY
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2020
·Vol. 95
·期 7
·1980-1988
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IF 2.75
Yushu He,Qianyue Huang,Pu Wang
BACKGROUND Deep eutectic solvents (DESs) derived from bio-available materials are promising eco-friendly solvents in the field of biocatalysis. However, the type of bio-based DES is still limited and its application in bioprocess has not been well-explored. We adopted a design strategy via the combination of choline and amino acids to synthesize novel bio-based DESs, aimed to enhance biocatalytic efficacy by exploiting the developed DESs as co-solvents. RESULTS Various bio-based DESs were synthesized, where the two components are both bio-available (choline and amino acids). Their performances in the bioreduction of 2-chloro-1-(3,4-difluorophenyl)ethanone (CFPO) were subsequently evaluated with recombinant Escherichia coli cells. The efficient asymmetric production of ( S )-2-chloro-1-(3,4-difluorophenyl)ethanol (( S )-CFPL) was successfully achieved in a developed choline acetate/lysine (ChAc/Lys)-containing medium. ChAc/Lys can strengthen coenzyme regeneration and properly improve cell membrane permeability during bioreduction, which account for high conversion. After optimized reaction parameters were conducted in the ChAc/Lys-buffer system, 87.0% ( S )-CFPL yield was observed with > 99.9% enantiomeric excess (ee) value at 1 mol L −1 CFPO content. The substrate loading in the established ChAc/Lys-buffer system was increased by 3.3-fold compared to aqueous medium. This bioprocess was also proved to be feasible at 500 mL preparative-scale with a satisfactory conversion. CONCLUSION ChAc/Lys bio-DES is a promising and biocompatible co-solvent. Introducing ChAc/Lys to the reaction system is an effective strategy for challenging high substrate loading for bioreduction. Our results give a valuable insight for developing green and benign sustainable bio-DESs for biotransformation. © 2020 Society of Chemical Industry
研究领域:
生物催化
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绿色化学
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合成生物学
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DOI
高影响因子
ANALYTICA CHIMICA ACTA
·
2019
·
IF 5.256
Yingying Zhang,Fanqiang Bu,Yanliang Zhao,Bing Zhao,Liyan Wang,Bo Song
Intracellular pH (pHi) plays an essential role in organelles . Fluorescent probe combined with fluorescence imaging analytical approach has been used for detection pH fluctuation due to high sensitivity and good photostability. Herein, a benzoindole-based colorimetric and naked-eye hemicyanine fluorescent probe 2,3-trimethy-3-[2,4-(dihyoxyl-4-yl)vinyl]-3 H -benzo[e]indole ( BiDD ) was developed in one step. Upon the decreasing of pH, BiDD exhibited strong a pH-dependent characteristic with p K a 4.98 and responded linearly within the pH range of 4.4–6.2. BiDD also showed high sensitivity and selectivity , colorimetric and fluorometric dual-modal response, high photostability, low cytotoxicity as well as good cell membrane permeability. More importantly, the probe was applied to sense and visualize the pH fluctuations in HeLa cells successfully by the fluorescence confocal microscope .
研究领域:
生物化学
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细胞生物学
·
分析化学
✓ 已验证
DOI
高影响因子
HUMAN & EXPERIMENTAL TOXICOLOGY
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2025
·
IF 3.2
Sicong Xie,Cheng Chang,Rongxing Jiang,Lifeng Wang,Yunli Yang,Zongjin Li,Yang Zhang
PurposeThis study investigated the mechanism by which Rosmarinic acid (RA) may alleviate doxorubicin (DOX)- induced cardiomyocyte apoptosis.MethodsThe target genes of RA, DOX-related differentially expressed genes, and GEO database related genes were retrieved by bioinformatics analyses. The results of these analyses were further intersected to identify candidate genes. The protein-protein interaction network was constructed to develop the pharmacophore model. The molecular docking was simulated to determine the core target B-cell lymphoma 2-like 1 (BCL2L1) for subsequent molecular mechanism investigation in vitro. The effects of DOX and RA on the apoptosis of H9c2 cells were assessed using the CCK8 assay. The present study investigated the effect of RA on DOX-induced oxidative stress in cardiomyocytes. This investigation was conducted using an ELISA test and a DCFH-DA probe. The JC-1 probe was utilized to assess the effect of RA on DOX-induced cardiomyocyte mitochondrial membrane permeability. A Western blot assay was conducted to ascertain the activation of multiple signaling molecules, including those belonging to the BCL-2 and caspase-3 families, within the apoptosis pathway.ResultsA total of 17 differentially expressed genes (DEGs) were screened, and five genes were selected as hub DEGs. A subsequent KEGG enrichment analysis revealed that these DEGs were significantly enriched in various biological processes and pathways, including the MAPK signaling pathway, autophagy, apoptosis, and the TNF signaling pathway. The pharmacophore model and molecular docking of five candidate targets with RA were successfully established. It is noteworthy that DOX treatment led to a suppression of SOD and GSH levels, an exacerbation of oxidative stress, and a promotion of cardiomyocyte apoptosis. Furthermore, it has been demonstrated to suppress mitochondrial membrane permeability. Subsequent RT-qPCR analysis of the hub genes revealed that only BCL2L1 exhibited significant alterations. Treatment with DOX altered the expression levels of apoptosis-associated proteins, BCL-2 family members, and caspase-3 family members. However, the administration of RA mitigated the deleterious effects of DOX on cardiomyocytes.ConclusionsThe protective effects of RA may against myocardial cell apoptosis are likely mediated through its activation of BCL2L1 and inhibition of caspase cascade protein expression in myocardial cells.
研究领域:
药理学
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生物信息学
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细胞生物学
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心血管研究
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2024
·
IF 5.7
Ruo-Fei Bai,Yi-Wei Wang,Shan-Shan Yang,Yu-Hao Zhang,Bo-Hang Zhou,Cong-Wei Zhou,Le Zhou
As part of our continuing research on propiolic acid derivatives, a series of benzyl propiolate derivatives and analogues were designed, synthesized, and investigated for inhibition activity in vitro and in vivo on phytopathogenic fungi, structure–activity relationship (SAR) and action mechanism. The results showed that most of the compounds had potent and broad-spectrum antifungal activity in vitro at 50 μg/mL. Among the compounds, 2-bromobenzyl propiolate (3h) displayed the highest comprehensive activity with total activity index (TAI) of 4.57 against all the eight test fungi followed by 3-fluorobenzyl propiolate (3c) (TAI = 4.53), superior to positive fungicides thiabendazole (TAI < 4.12) and/or azoxystrobin (TAI < 2.90). Relative to the other fungi, Fusarium solani and Fusarium graminearum revealed higher total susceptibility indexes (TSI) of 11.1 and 8.98, respectively, for all compounds. 3h and 3g (4-chlorobenzyl propiolate) gave the smallest EC50 values of 0.86 and 0.67 μg/mL against F. solani and F. graminearum, respectively, superior or comparable with thiabendazole and azoxystrobin. As a representative, 3h at 200 μg/mL displayed 100% protection on F. solani infections on potatoes over 7 days and high safety for plant growth. In antifungal mechanism, 3h was able to change mycelial morphology, destroy the structures of both hypha and cell membrane, increase the intracellular ROS level, decrease the intracellular mitochondrial membrane potential level, and change the permeability of the cell membrane. The SAR showed that ethynyl is a key group for the activity, and the presence of halogen atoms at the 2-site of the benzene ring can significantly improve the activity in most cases. Thus, benzyl propiolate can be considered a novel antifungal lead compound, while 3h can be considered a promising fungicide candidate to develop new agricultural fungicides.
研究领域:
农业化学
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植物病理学
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药物化学
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DOI
PubMed
高影响因子
Polymer Chemistry
·
2017
·Vol. 8
·期 42
·6520-6526
·
IF 5.375
Jian Chen,Weibang Zhong,Mingju Xue,Hong Wang,Maolin Yu,Peisheng Zhang,Pinggui Yi
Superior photoswitchable fluorescent polymer nanoparticles (PFPNs) are highly desirable for photo-rewritable data storage and ultrahigh-resolution bioimaging. Herein, 2-(3′,3′-dimethyl-6-nitrospiro[chromene-2,2′-indolin]-1′-yl)ethyl 2-(((dodecylthio)-carbonothioyl)thio)-2-methylpropanoate (SPTTC), a novel photochromic spiropyran-based reversible addition–fragmentation chain transfer (RAFT) reagent, and 5-dimethylaminonaphthalene-N-allyl-1-sulfonamide (DNS), the energy-level matched green fluorescent dye, were firstly synthesized. Then, they are used as donor and acceptor of the designed fluorescence resonance energy transfer (FRET) system to help fabricate superior dual-color PFPNs via a simple one-pot RAFT miniemulsion method. Thanks to its multiple merits such as the photochromic property, improved miscibility, and the ability to control polymerization rate, not only did the designed SPTTC provide the PFPNs with superior photoswitchable fluorescence properties such as high energy transfer efficiency (up to 91%), high dual-color contrast (green and red), rapid photoresponsiveness (2–4 min) and outstanding photoreversibility upon irradiation with UV and visible light, but it also endowed PFPNs with controllable molecular weight and narrow polydispersity index (PDI), excellent cell membrane permeability and long-term fluorescence stability. Moreover, the as-prepared PFPNs were successfully used for rewritable fluorescence patterning and intracellular dual-color imaging due to its prominent properties.
研究领域:
高分子化学
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生物成像
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纳米医学
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光响应材料
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分子诊断
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DOI
高影响因子
PHARMACEUTICAL CHEMISTRY JOURNAL
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2024
·Vol. 57
·期 8
·1179-1188
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IF 0.8
Pan Miao,Yuan Jia,Tang Qin,Wu Yajing,Peng Yu,Zhang Jinyin,Ma Hang,Li Xuegang
Antibiotic resistance is a major problem in the treatment of Helicobacter pylori (H. pylori). Berberine (BBR) has proven to be a promising alternative, though it is less effective than antibiotics. Structurally modified BBR might improve the anti-H. pylori activity. In this study, 8-octyl berberine (OBBR), a BBR derivative, was investigated for the activity and mechanism of action against H. pylori. The results showed that the anti-H. pylori activity of OBBR was significantly higher than that of BBR (about 64 times) and close to amoxicillin. Surprisingly, OBBR was not resistant to H. pylori after 45 generations of induction and showed synergistic effect with amoxicillin in vitro. Regarding the mechanism, OBBR changed the morphological structure of bacteria and caused the outgrowth of phosphatidylserine on the cell membrane, thereby increasing its permeability. Moreover, OBBR inhibited the urease activity, down-regulated the mRNA levels of flagellar genes flaA and flaB, and reduced the motility of H. pylori, thus inhibiting intra-gastric colonization. In an animal model of H. pylori infection, OBBR was found to have a certain effect on the clearance of H. pylori in mice. An excellent anti-H. pylori activity and low drug resistance of OBBR suggest that structural modification of the BBR scaffold may be a favorable approach to the development of promising antibiotics for the treatment of H. pylori.
研究领域:
微生物学
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药理学
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药物化学
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传染病学
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分子生物学
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DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2024
·
IF 5.7
Bohang Zhou,Juan Fu,Yuhao Zhang,Ruofei Bai,Yiwei Wang,Yiwei Yang,Yingmei Li,Le Zhou
Replacing old pesticides with new pesticide varieties has been the main means to solve pesticide resistance. Therefore, it is necessary to research and develop new antifungal agents for plant protection. In this study, a series of pyridinecarbaldehyde phenylhydrazone derivatives were designed and evaluated for their inhibition activity on plant pathogenic fungi to search for novel fungicide candidates. Picolinaldehyde phenylhydrazone (1) and nicotinaldehyde phenylhydrazone (2) were identified as promising antifungal lead scaffolds. The 4-fluorophenylhydrazone derivatives (1a and 2a) of 1 and 2 showed highly effective and broad-spectrum inhibition activity in vitro on 11 phytopathogenic fungi with EC50 values of 0.870–3.26 μg/mL, superior to the positive control carbendazim in most cases. The presence of the 4-fluorine atom on the phenyl showed a remarkable activity enhancement effect. Compound 1a at 300 μg/mL provided almost complete protection against infection of Alternaria solani on tomatoes over the post-treatment 9 days and high safety to germination of plant seeds. Furthermore, 1a showed strong inhibition activity with an IC50 value of 0.506 μg/mL on succinate dehydrogenase in A. solani. Molecular docking showed that both 1a and 2a can well bind to the ubiquinone-binding region of SDH by the conventional hydrogen bond, carbon–hydrogen bond, π–π or π–amide interaction, π–alkyl interaction, X---F (X = N, C, or H) interaction, and van der Waal forces. Meanwhile, scanning and transmission electron analysis displayed that 1a destroyed the morphology of mycelium and the structure of the cell membrane of A. solani. Fluorescent staining analysis revealed that 1a changed the mitochondrial membrane potential and cell membrane permeability. Thus, pyridinecarbaldehyde phenylhydrazone compounds emerged as novel antifungal lead scaffolds, and 1a and 2a can be considered promising candidates for the development of new agricultural fungicides.
研究领域:
植物病理学
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分子生物学
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农业化学
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植物保护
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DOI
PubMed
高影响因子
CHEMOSPHERE
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2024
·
IF 8.1
Renle Xu,Yuhang Lou,Yanqing Gao,Shibin Shang,Zhanqian Song,Kerang Huang,Luqi Li,Lei Chen,Jian Li
To mitigate the impact of traditional chemical pesticides on environment, and achieve sustainable crop protection, 24 eco-friendly rosin-based sulfonamide derivatives were synthesized and developed. The in vitro activity assessment showed that compound 4X (Co. 4X) exhibited excellent fungicidal activity against V. mali (EC 50 = 1.106 μg/mL), marginally surpassing the positive control carbendazim (EC 50 = 1.353 μg/mL). In vivo investigations suggested that Co. 4X exhibited moderate efficacy in mitigating V. mali infection in both apple trees and apples. Physiological assessments revealed that Co. 4X induced severe ultrastructural damage to the mycelium, heightened cell membrane permeability, and inhibited SDH protein activity. Subsequent biosafety evaluations affirmed the environment-friendly of Co. 4X on Zebrafish (LC 50(96h) = 25.176 μg/mL). Toxicological research revealed that Co. 4X caused damage to the cells of Zebrafish gills, liver, and intestines, resulting in impaired respiratory, detoxification, digestion, and absorption functions of Zebrafish. In summary, the findings of this study contribute to a deeper understanding of the toxicity mechanisms of novel pesticides, decreasing environmental risks caused by traditional chemical pesticides, and improving the effective management of novel pesticide applications.
研究领域:
植物保护
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毒理学
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环境科学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Biochemistry and Cell Biology
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2024
·
IF 2.4
Wei Yan,Ruolan Wu,Yingying Lee,Liqun Xu,Xiao Li,Junwei Li,Ronghao Deng,Xing Fan,Yilang Wu,Haibao Zhu,Aihua Mao,Jianxin Shen,Chi-ju Wei
Enucleated cells, also known as cytoplasts, are valuable tools with a wide range of applications. However, their potential for bio-engineering is greatly restricted by the short lifespan. We postulated that the enucleation process damages the integrity of the plasma membrane and thus activates a cell death program(s). The results showed that a tiny hole was generated transiently on the plasma membrane when the nucleus was spun off, while force-gated ion channels were activated in response to the pulling by the nucleus. Influx of extracellular calcium stimulated the opening of calcium channels and the release of calcium from endoplasmic reticulum and mitochondria. Long lasting calcium transient increased protein phosphorylation and activated caspase 9 and calpain proteinase activities. Subsequently, mitochondria membrane permeability and Reactive Oxygen Species (ROS) levels were significantly elevated, which eventually led to eryptosis-like cell death. When extracellular calcium was maintained at optimal concentration, the lifespan of enucleated cells was extended; however, huge amounts of vacuoles appeared in the cytoplasm, possibly derived from enlarged autophagosomes. Inhibition of vacuolation by inhibitors of autophagy or in co-culture with primary muscle cells did not rescue cells dying from the paraptosis-like pathway. These results offer valuable insights for further investigation into the intricate mechanisms underlying enucleated cell death.
研究领域:
细胞生物学
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干细胞研究
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分子生物学
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钙信号传导
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）