CARBON
·
2025
·
IF 11.6
Junzhu Yang,Junchen Liu,Yi Zhang,Wei Pei,Qi Xia,Sanyang Han,Yuan Lu
Efficient regeneration of the coenzymes NADH and NADPH is crucial for sustaining biocatalytic processes, particularly in driving the biocatalysis reaction. In this study, the photocatalytic properties of alkali-doped graphitic carbon nitrates were explored to achieve efficient NAD(P)H regeneration. g-C 3 N 4 doped with potassium (KOH), sodium (NaOH), and calcium (Ca(OH) 2 ) was synthesized and characterized, showing significant enhancements in light absorption, charge separation, and photogenerated electron transport. Among the synthesized photocatalysts, KOH-doped g-C 3 N 4 (KCN) exhibited the best photocatalytic performance, regenerating 95 % NADH and 92 % NADPH within 30 min. This result compares favorably with those reported in previous studies. Based on this superior performance, K-0.2 was further applied to the in vitro CO 2 reduction to formate as a proof of concept. To clarify the mechanistic insights of the improved photocatalytic performance of KCN, the chemical model of g-C 3 N 4 and KCN was established, and DFT calculations were performed to reveal the electronic structure modifications responsible for the enhanced photocatalytic activity. Furthermore, to expand the light utilization capability of the system, upconversion nanoparticles (UCNPs) were incorporated into the system to utilize near-infrared light (980 nm), which successfully achieved NADH regeneration under near-infrared excitation and extended the light absorption range of the photocatalytic system. Overall, this study demonstrated that alkali-doped g-C 3 N 4 offered a highly efficient platform for NAD(P)H regeneration, and the integration of UCNPs further enriched the coenzyme regeneration scenario, suggesting a promising strategy for advancing sustainable coenzyme regeneration technologies.
研究领域:
生物催化
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光化学
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分子生物学
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可持续能源
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酶工程
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 9
·8265
·
IF 5.6
Jing Li,Jianchao Zhang,Yan Zhu,Lukman O. Afolabi,Liang Chen,Xuesong Feng
Triple-negative breast cancer (TNBC) has been clearly recognized as a heterogeneous tumor with the worst prognosis among the subtypes of breast cancer (BC). The advent and application of current small-molecule drugs for treating TNBC, as well as other novel inhibitors, among others, have made treatment options for TNBC more selective. However, there are still problems, such as poor patient tolerance, large administration doses, high dosing frequency, and toxic side effects, necessitating the development of more efficient and less toxic treatment strategies. High expression of Nrf2, a vital antioxidant transcription factor, often promotes tumor progression, and it is also one of the most effective targets in BC therapy. We found that in MDA-MB-231 cells and SUM159 cells, brusatol (BRU) combined with polydatin (PD) could significantly inhibit cell proliferation in vitro, significantly downregulate the expression of Nrf2 protein as well as the expression of downstream related target genesHeme Oxygenase-1 (HO-1)andNAD(P)H dehydrogenase, quinone 1 (NQO1), and promote reactive oxygen species (ROS) levels to further strengthen the anti-tumor effect. Furthermore, we discovered in our in vivo experiments that by reducing the drug dosage three times, we could significantly reduce tumor cell growth while avoiding toxic side effects, providing a treatment method with greater clinical application value for TNBC treatment.Keywords:breast cancer;brusatol;polydatin;Nrf2;HO-1;NQO1;ROS
研究领域:
肿瘤学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
ACS Sustainable Chemistry & Engineering
·
2021
·
IF 8.198
Hai-Peng Li,Zhi-Neng You,Yuan-Yang Liu,Gao-Wei Zheng,Heng Gong,Yiming Mo,Ning Zhu,Yun-Peng Bai,Jian-He Xu
Water-forming NAD(P)H oxidases (NOXs) constitute a clean NAD(P)+ regeneration strategy for NAD(P)+-dependent biotransformations to produce high value-added chemicals because they only consume oxygen and generate water. However, the application of NOXs is still challenging because of limited oxygen transfer in batch reactions. Here, we report an efficient continuous-flow microreactor (CFMR) to improve the oxygen transfer and reaction performance in NAD+-dependent chenodeoxycholic acid oxidation catalyzed by 7α-hydroxysteroid dehydrogenase (7α-HSDH) for the production of 7-oxo-lithocholic acid, a key precursor of ursodeoxycholic acid. The recycling efficiency of NAD+ by NOX from Streptococcus mutans (SmNOX) was significantly improved in this CFMR. Compared with a conventional batch stirred tank reactor, the space–time yield of production of 7-oxo-lithocholic acid was increased by 96-fold. Furthermore, the total turnover number of NAD+ was improved 10-fold, and the enzyme consumption number was decreased 7-fold. Combining the NOX/O2 system with this microreactor technology provides a general platform that enables various NAD(P)+-dependent biotransformations in a green and sustainable manner, which will be helpful in the design of ecofriendly bioprocesses for production of functional chemicals on a large scale.
研究领域:
生物化学
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合成生物学
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绿色化学
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产品关联
DOI
高影响因子
BIOORGANIC CHEMISTRY
·
2023
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IF 5.1
Zhishang Zhang,Wenqing Li,Haorui Wu,Zhuangfeng Liu,Huaiyi Huang
The challenge of antibiotic resistance worldwide has brought an urgent need to explore novel drugs for bacterial infections. Antimicrobial photodynamic therapy has been proven to be a potential antimicrobial modality but is limited by biofilms. In this study, we synthesized three cationic photosensitizers with strong photoinduced antimicrobial and antibiofilm activities toward gram-positive Staphylococcus aureus . The indole–pyridine compounds illustrated multiple type I/II photosensitization and coenzyme NAD(P)H photocatalytic activity upon excitation. A mechanistic study showed that intracellular reactive oxygen generation and NAD(P)H oxidation caused membrane damage, leading to protein/nucleus acid leakage. This research provides insights into the development of novel chemotherapeutics with synergetic photodynamic and photocatalytic reactivity.
研究领域:
药学
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微生物学
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光化学
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抗菌研究
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产品关联
DOI
PubMed
高影响因子
Redox Biology
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2024
·
IF 10.7
Bi-Xin Xu,Tian-Yu Hu,Jin-Biao Du,Tao Xie,Ya-Wen Xu,Xin Jin,Si-Tao Xu,Hao-Wen Jin,Guangji Wang,Jiankun Wang,Le Zhen
Redox-responsive hydropersulfide prodrugs are designed to enable a more controllable and efficient hydropersulfide (RSSH) supply and to thoroughly explore their biological and therapeutic applications in oxidative damage. To obtain novel activation patterns triggered by redox signaling, we focused on NAD(P)H: quinone acceptor oxidoreductase 1 (NQO1), a canonical antioxidant enzyme, and designed NQO1-activated RSSH prodrugs. We also performed a head-to-head comparison of two mainstream structural scaffolds with solid quantitative analysis of prodrugs, RSSH, and metabolic by-products by LC-MS/MS, confirming that the perthiocarbamate scaffold was more effective in intracellular prodrug uptake and RSSH production. The prodrug was highly potent in oxidative stress management against cisplatin-induced nephrotoxicity. Strikingly, this prodrug possessed potential feedback activation properties by which the delivered RSSH can further escalate the prodrug activation via NQO1 upregulation. Our strategy pushed RSSH prodrugs one step further in the pursuit of efficient release in biological matrices and improved druggability against oxidative stress.
研究领域:
药学
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生物化学
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分子生物学
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毒理学
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DOI
PubMed
高影响因子
Chemical Biology & Drug Design
·
2020
·Vol. 96
·期 6
·1433-1446
·
IF 2.548
Yibing Guo,Liancheng Xu,Changchun Ling,Tao Yang,Wenjie Zheng,Jin Lv,Qingsong Guo,Bohua Chen
Eighteen new β-carboline-based indole-4,7-quinone derivatives ( 12a–i and 13a–i ) were designed and synthesized, and their in vitro and in vivo antiproliferative activities were studied. Most of target compounds showed strong inhibition on three human tumor cells' proliferation. In particular, the most active compound 13g not only displayed more prominent antiproliferative activities than β-lapachone, a clinical antitumor candidate, but also exerted significant NAD(P)H: quinone-oxidoreductase-1 (NQO1) inhibitory activity and NQO1-dependent cytotoxicity in HT29 cells. Furthermore, 13g dose-dependently induced high ROS levels in HT29 cells, and selectively inhibited cancer cell but not non-tumor colon cell proliferation in vitro. Importantly, 13g promoted HT29 cell apoptosis and DNA damage by regulating relative apoptotic proteins and H2AX expression. Finally, 13g displayed significant growth inhibition of HT29 human colorectal adenocarcinoma xenograft in mice without overt toxicity.
研究领域:
药理学
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肿瘤学
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药物化学
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DOI
PubMed
高影响因子
CHEMISTRY-A EUROPEAN JOURNAL
·
2021
·Vol. 28
·期 3
·e202103346
·
IF 5.236
Zhongxian Fan,Jiaen Xie,Tumpa Sadhukhan,Chao Liang,Can Huang,Wenqing Li,Tingxuan Li,Pingyu Zhang,Samya Banerjee,Krishnan Raghavachari,Huaiyi Huang
Graphical Four novel Ir(III) photo-catalysts ( Ir1 – Ir4 ) were synthesized and applied for photocatalytic cancer therapy. Upon blue and green light irradiation, these photocatalysts generated singlet oxygen and induced rapid photo-catalytic oxidation of the cellular coenzymes NAD(P)H. Ir2 triggered promising photo-induced anticancer activity via induction of intracellular redox imbalance and exhibited ideal in vivo photo-induced catalytic anticancer activity. Four photo-catalysts of the general formula [Ir(CO6/ppy) 2 (L)]Cl where CO6=coumarin 6 ( Ir1 – Ir3 ), ppy=2-phenylpyridine ( Ir4 ), L=4′-(3,5-di-tert-butylphenyl)-2,2′ : 6′,2′′-terpyridine ( Ir1 ), 4′-(3,5-bis(trifluoromethyl)phenyl)-2,2′ : 6′,2′′-terpyridine ( Ir2 and Ir4 ), and 4-([2,2′ : 6′,2′′-terpyridin]-4′-yl)-N,N-dimethylaniline ( Ir3 ) were synthesized and characterized. These photostable photo-catalysts ( Ir1 – Ir3 ) showed strong visible light absorption between 400–550 nm. Upon light irradiation (465 and 525 nm), Ir1 – Ir3 generated singlet oxygen and induced rapidly photo-catalytic oxidation of cellular coenzymes NAD(P)H. Ir1 – Ir3 showed time-dependent cellular uptake with excellent intracellular retention efficiency. Upon green light irradiation (525 nm), Ir2 provided a much higher photo-index (PI=793) than the clinically used photosensitizer, 5-aminolevulinicacid (5-ALA, PI>30) against HeLa cancer cells. The observed necro-apoptotic anticancer activity of Ir2 was due to the Ir2 triggered photo-induced intracellular redox imbalance (by NAD(P)H oxidation and ROS generation) and change in the mitochondrial membrane potential. Remarkably, Ir2 showed in vivo photo-induced catalytic anticancer activity in mouse models.
研究领域:
癌症研究
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光化学
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材料科学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Mingye Li,Yuyu Dong,Zheng Wang,Yanjun Zhao,Yujie Dai,Baoxin Zhang
Glucose-6-phosphate dehydrogenase (G6PD) is a promising target in cancer therapy. However, poor cellular uptake and off-target toxicity impeded the clinical translation of a canonical G6PD inhibitor (6-aminonicotinamide/6AN). Here, we report a prodrug strategy to address this issue. The tailored 6AN prodrug contains an azo-bearing protection moiety. The hydrophobic prodrug showed increased cellular uptake than 6AN and is vulnerable to hypoxia, resulting in NAD(P)H quinone dehydrogenase 1 (NQO1)-triggered cleavage of azo bonds. Intriguingly, the prodrug shows configuration-dependent anti-cancer potency. Despite the lower thermodynamic stability, the cis isomer showed enhanced cellular uptake compared to the trans counterpart due to the increased aqueous solubility. Moreover, the boosted potency of cis isomer compared to the trans isomer resulted from the enhancement of NOQ1-catalyzed 6AN release under hypoxia, a hallmark of solid tumors. The discovery of hypoxia-responsive 6AN prodrugs in the current work opens new avenues of G6PD-targeting cancer medicines via redox manipulation.
研究领域:
药学
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癌症研究
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药物递送系统
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氧化还原生物学
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产品关联
DOI
PubMed
高影响因子
Synthetic and Systems Biotechnology
·
2024
·
IF 4.4
Zetian Qiu,Xiaohui Liu,Jie Yu,Yushuo Zhao,Guang-Rong Zhao,Shengying Li,Kun Liu,Lei Du,Li Ma
Benzyl and phenylpropanoid acids are widely used in organic synthesis of fine chemicals, such as pharmaceuticals and condiments. However, biocatalysis of these acids has received less attention than chemical synthesis. One of the main challenges for biological production is the limited availability of alcohol dehydrogenases and aldehyde dehydrogenases. Environmental microorganisms are potential sources of these enzymes. In this study, 129 alcohol dehydrogenases and 42 aldehyde dehydrogenases from Corynebacterium glutamicum , Pseudomonas aeruginosa , and Bacillus subtilis were identified and explored with various benzyl and phenylpropanoid alcohol and aldehyde substrates, among which four alcohol dehydrogenases and four aldehyde dehydrogenases with broad substrate specificity and high catalytic activity were obtained. Moreover, a cascade whole-cell catalytic system including ADH-90, ALDH-40, and the NAD(P)H oxidase LreNox was established, which showed high efficiency in converting cinnamyl alcohol and p -methylbenzyl alcohol into the respective carboxylic acids. Remarkably, this biocatalytic system can be easily scaled up to gram-level production, facilitating preparation purposes.
研究领域:
生物技术
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生物化学
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有机化学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Wenting Li,Jihui Zhou,Yangyang Zhang,Shikai Liu,Rumin Li,Shili Gai,He Ding,Lei Zhong,Piaoping Yang
Photothermal-enhanced chemodynamic therapy (CDT) based on the Fenton reaction has been widely studied as a safe, tumor-specific, and highly effective nanomedicine therapy. Herein, a collective hyperthermia-facilitated glutathione (GSH) inhibition strategy for boosted oxidative stress treatment was presented using mesoporous Prussian blue (MPB NPs) as a multifunctional carrier and loading β-lapachone (Lap) as an oxidative mediator. A phase transfer catalyst (lauric acid, La) was co-packed for preventing drug leakage and achieving temperature-controlled drug release. After biocompatible decoration by external encapsulation with polyethylene glycol (PEG), the MPB-Lap/La@PEG nanocatalysts (Mlalp NCs) were rationally constructed. Upon 808 nm light irradiation, the Mlalp NCs showed a good photothermal effect with temperature increases for directly damaging tumor cells and accelerating the release of Lap. Significantly, the expression of NAD(P)H: quinone oxidoreductase-1 (NQO1) in cells could increase and generate more hydrogen peroxide (H 2 O 2 ) with Lap and reduce the level of GSH concurrently, forming a hyperthermia-facilitated glutathione inhibition strategy. Most importantly, the hyperthermia also accelerated the Fenton reaction rate, resulting in an enhanced CDT effect. In addition, the Mlalp NCs also equipped with excellent T 1 -weighted magnetic resonance imaging properties. To sum up, this work displays a collective hyperthermia-facilitated glutathione inhibition strategy for boosted oxidative stress treatment.
研究领域:
纳米医学
·
癌症治疗
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材料科学
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生物医学工程
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产品关联
DOI
高影响因子
XENOBIOTICA
·
2018
·
IF 1.857
Yue Li,Yujuan Fan,Huizong Su,Qian Wang,Guo-Fu Li,Yiyang Hu,Jian Jiang,Bo Tan,Furong Qiu
Tanshinone I (TSI) is a lipophilic diterpene in Salvia miltiorrhiza with versatile pharmacological activities. However, metabolic pathway of TSI in human is unknown.In this study, we determined major metabolites of TSI using a preparation of human liver microsomes (HLMs) by HPLC-UV and Q-Trap mass spectrometer. A total of 6 metabolites were detected, which indicated the presence of hydroxylation, reduction as well as glucuronidation.Selective chemical inhibition and purified cytochrome P450 (CYP450) isoform screening experiments revealed that CYP2A6 was primarily responsible for TSI Phase I metabolism. Part of generated hydroxylated TSI was glucuronidated via several glucuronosyltransferase (UGT) isoforms including UGT1A1, UGT1A3, UGT1A7, UGT1A9, as well as extrahepatic expressed isoforms UGT1A8 and UGT1A10. TSI could be reduced to a relatively unstable hydroquinone intermediate by NAD(P)H: quinone oxidoreductase 1 (NQO1), and then immediately conjugated with glucuronic acid by a panel of UGTs, especially UGT1A9, UGT1A1 and UGT1A8. Additionally, NQO1 could also reduce hydroxylated TSI to a hydroquinone intermediate, which was immediately glucuronidated by UGT1A1.The study demonstrated that hydroxylation, reduction as well as glucuronidation were the major pathways for TSI biotransformation, and six metabolites generated by CYPs, NQO1 and UGTs were found in HLMs and S9 subcellular fractions.
研究领域:
药理学
·
代谢
·
药物代谢
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Qi Liang,Rongjie Guo,Jia-Ruei Tsao,Yun He,Chenchen Wang,Jiaxuan Jiang,Di Zhang,Taige Chen,Tingting Yue,Kai Hu
Dry eye disease (DED) is a multifactorial disease, and oxidative stress plays a crucial role in its pathogenesis. Recently, multiple studies have shown that upregulation of autophagy can protect the cornea from oxidative stress damage. The present study investigated the therapeutic effects of salidroside, the main component of Rhodiola crenulata , in both in vivo and in vitro dry eye models. The results showed that topical eye drop treatment with salidroside restored corneal epithelium damage, increased tear secretion, and reduced cornea inflammation in the DED mice. Salidroside activated autophagy through AMP-activated protein kinase (AMPK)-sirtuin-1 (Sirt1) signaling pathway, which promoted the nuclear translocation of nuclear factor erythroid-2-related factor 2 (Nrf2) and increased the expression of downstream antioxidant factors heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1). This process restored antioxidant enzyme activity, reduced reactive oxygen species (ROS) accumulation, and alleviated oxidative stress. The application of autophagy inhibitor chloroquine and AMPK inhibitor Compound C reversed the therapeutic efficacy of salidroside, validating the above findings. In conclusion, our data suggest that salidroside is a promising candidate for DED treatment.
研究领域:
药理学
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眼科
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）