CHIRALITY
·
2024
·Vol. 36
·期 5
·e23672
·
IF 2.8
Chen Chen,Yangfeng Peng,Yongming Wei,Mengyuan Liu,Yu Wang,Siqi Xiong,Huiyi Li,Quan He
Hydroxychloroquine (HCQ), 2-([4-([7-Chloro-4-quinolyl]amino)pentyl]ethylamino)ethanol, exhibited significant biological activity, while its side effects cannot be overlooked. The RP-HPLC enantio-separation was investigated for cost-effective and convenient optical purity analysis of HCQ. The thermodynamic resolution of Rac-HCQ, driven by enthalpy and entropy, was achieved on the C18 column using Carboxymethyl-β-cyclodextrin (CM-β-CD) as the chiral mobile phase agent (CMPA). The effects of C CM-β-CD , pH, and triethylamine (TEA) V% on the enantio-separation process were explored. Under the optimum conditions at 24°C, the retention times for the two enantiomers were t R 1 = 29.39 min $$ {t}_{R1}=29.39\ \min $$ and t R 2 = 32.42 min $$ {t}_{R2}=32.42\ \min $$ , resulting in R s = 1.87 $$ {R}_s=1.87 $$ . The resolution via diastereomeric salt formation of Rac-HCQ was developed to obtain the active pharmaceutical ingredient of single enantiomer S-HCQ. Di-p-Anisoyl-L-Tartaric Acid (L-DATA) was proved effective as the resolution agent for Rac-HCQ. Surprisingly, it was found that refluxing time was a key fact affecting the resolution efficiency, which meant the kinetic dominate during the process of the resolution. Four factors—solvent volume, refluxing time, filtration temperature, and molar ratio—were optimized using the single-factor method and the response surface method. Two cubic models were established, and the reliability was subsequently verified. Under the optimal conditions, the less soluble salt of 2L-DATA:S-HCQ was obtained with a yield of 96.9% and optical purity of 63.0%. The optical purity of this less soluble salt increases to 99.0% with a yield of 74.2% after three rounds recrystallization.
研究领域:
药物化学
·
分析化学
·
制药工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SEPARATION AND PURIFICATION TECHNOLOGY
·
2024
·
IF 8.1
Boqiang Gao,Haoge Liang,Jie Wang,Yan Huang,Jingzhen Wang,Jia Song,Pan Hu,Hu Yang,Shuanglong Ma
Hydroxychloroquine (HCQ) as an antiviral pharmaceutical has been widely detected in the aquatic environment. Adsorption is an effective method for removal of HCQ, but the quantitative study of the adsorption interactions is unclear. In this study, a carboxylated lignin-based sponge (PLC) was fabricated, and the adsorption contributions of electrostatic attraction (EA), hydrogen bond (HB), and π-π electron donor–acceptor (π-π EDA) interactions were quantitatively investigated. The results showed that PLC exhibited excellent adsorption performance under wide pH range (4.0 < pH < 11.0), with the highest adsorption capacity of 0.165 mmol/g. Inhibitor and molecular probe experiments showed that EA and HB were the main contributors to adsorption at neutral and basic pH ranges, respectively. A linear correlation model of the carboxyl groups of lignin-based sponges with the adsorption capacity of EA, HB, and π-π EDA interactions of HCQ ( R 2 > 0.822) and three molecular probes ( R 2 > 0.749) was established, respectively. The optimal adsorption capacity was achieved by the synergistic combination of the deprotonated carboxyl of PLC with the HB of Ka1 amino, EA of Ka2 amino, and the π-π EDA of the quinoline ring. This study provided a new strategy for the quantitative construction of structure–activity relationships of adsorbents.
研究领域:
环境科学
·
材料科学
·
药学
✓ 已验证
产品关联
DOI
高影响因子
Environmental Science-Water Research & Technology
·
2025
·
IF 3.1
Kunlun Yang,Dengyang Wang,Yuxuan Yang,Youxiang Pan,Mengsi Wu,Hengfeng Miao
In this study, a novel catalytic ceramic membrane (ITC-2-800@CM) was modified with Fe/N/S doped cyanobacterial biochar catalysts to adjust its surface morphology and properties to significantly enhance its organic pollutant removal performance and membrane anti-fouling ability. Specifically, the biochar modification further increased the roughness and hydrophobicity of the pristine ceramic membrane, apparently improving the adsorption capacity of hydroxychloroquine (HCQ) causing membrane fouling. Although sacrificing partial membrane permeability, based on the strong peroxymonosulfate (PMS) activation performance of cyanobacterial biochar, abundant reactive oxygen species were generated and degraded the organic pollutants adsorbed on the surface and pore of ITC-2-800@CM. Hence, the efficient synergistic effect between in situ adsorption, filtration and PMS activation further enhanced hydroxychloroquine removal and membrane anti-fouling performance, especially under a long operation. The actual lake water treatment experiments demonstrated that the ITC-2-800@CM–PMS system could stably remove more than 90% of HCQ and reduce the reversible and irreversible membrane fouling resistance by 81.57% and 60.68% as compared to the pristine CM/PMS system. Furthermore, the treated effluent showed significant reduction in total nitrogen, dissolved organic carbon and UV254 concentrations, highlighting the high applicability of the ITC-2-800@CM–PMS system in practical polluted water treatment. This improvement can decrease the need for frequent membrane cleaning during water treatment, thereby reducing operational costs. This research not only provided an easy method for ceramic membrane modification to extend its operational lifespan, but also offered deeper insights into the synergistic effect between in situ filtration and advanced oxidation.
研究领域:
环境科学
·
材料科学
·
水处理工程
✓ 已验证
产品关联
DOI
高影响因子
FOOD CHEMISTRY
·
2024
·
IF 8.5
Quan Ma,Dong Li,Yicheng Ren,Yanpei Chen,Jing Huang,Bin Wu,Qingqing Wang,Zisheng Luo
Autophagy (AU) and programmed cell death (PCD) are dynamically regulated during tomato fruit defense against Botrytis cinerea , which are also manipulated by pathogenic effectors to promote colonization. Present study demonstrated that the enhanced defense induced by transient inhibition on AU by hydroxychloroquine (HCQ) facilitated the restriction of B. cinerea lesion on postharvest tomato. Pre-treatment of 2 mM (16.08 ± 3.42 cm at 7 d) and 6 mM (7.80 ± 2.39 cm at 7 d) HCQ inhibited the lesion development of B. cinerea compared with Mock treatment (50.02 ± 7.69 cm at 7 d). Transient inhibition of AU induced expression of fungal defense and transcriptional regulation related genes, but attenuated reactive oxygen species (ROS) burst gene expression. The ROS-induced PCD was compromised by HCQ with promoted ROS scavenging. The transient pre-treatment of HCQ slightly inhibited AU which triggered the feedback loop that enhanced the autophagic activity defensing against B. cinerea infection.
研究领域:
植物病理学
·
分子生物学
·
农业科学
✓ 已验证
DOI
PubMed
高影响因子
DALTON TRANSACTIONS
·
2024
·
IF 3.5
Linming Li,Yan Chen,Ming Zhang,Suying Li,Shuaiqi Feng,Yan-Qin He,Ning Zhang,Zhifang Liu,Meifeng Liu,Qing-Peng Wang
Protective autophagy is a promising target for antitumor drugs exploration. A hydroxychloroquine (HCQ) platinum(IV) complex with autophagy suppressing potency was developed, which displayed potent antitumor activities with a TGI of 44.2% against 4T1 tumors in vivo and possessed rather lower toxicity than cisplatin. Notably, it exhibited satisfactory antimetastatic activities toward lung pulmonary metastasis models with inhibition rate of 49.6%, which was obviously more potent than CDDP (21.6%). Mechanism detection revealed that it caused serious DNA damage and upregulated the expression of γ-H2AX and p53. More importantly, the incorporation of autophagy inhibitor HCQ endowed platinum(IV) complex with potent autophagy impairing properties by perturbing lysosomal function in tumor cells, which promoted apoptosis synergistically with the DNA injury. Then, the impaired autophagy further led to the suppression of hypoxia and inflammation in tumor microenvironment by downregulating ERK1/2, HIF-1α, iNOS, caspase1 and COX-2. Adaptive immune response was improved by inhibiting immune checkpoint PD-L1, and further increasing CD4+ and CD8+ T cells in tumors. Then, tumor metastasis was effectively inhibited by restraining angiogenesis through inhibiting VEGFA, MMP-9, and CD34.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOPATHOLOGY
·
2025
·
IF 3.1
Chengyan Xia,Xiansu Wang,Miss Zeqi Qi,Miss Fenghua Liu,Miss Dongxue Li,Miss Xiaolin Zhang,Libo Zhang,Delu Wang,Zhuo Chen
Gray mold is an important disease of crops and is widespread, harmful, difficult to control, and prone to developing fungicide resistance. Screening new fungicides is an important step in controlling this disease. Hydroxychloroquine is an anti-inflammatory and anti-malarial agent, which has shown marked inhibitory activity against many fungi in medicine. This study evaluated the inhibitory activity of hydroxychloroquine against several phytopathogenic fungi, finding a half-maximal effective concentration of 113.82 μg/ml against the hyphal growth of Botrytis cinerea , with significant in-vivo curative effects of 92.37% or 78.37% for gray mold on detached tomato leaves or fruits at 10.0 or 200.0 mg/ml, respectively. Ultrastructural studies indicated that hydroxychloroquine induced collapse of hyphae, with a wrinkled surface, unclear organelle boundaries, and organelle disintegration. Transcriptomic assays revealed that hydroxychloroquine could affect the expression of metabolism-related genes. Molecular docking and molecular dynamics analyses indicated that hydroxychloroquine bound to glucose-methanol-choline oxidoreductase, with low free energy value of −11.4 kcal/mol. Cell membrane permeability assays and hyphal staining confirmed that hydroxychloroquine damaged the cell membrane, causing leakage of hyphal contents and disturbing cell function. Biochemical assays indicated that hydroxychloroquine reduced the concentration of soluble proteins and reducing sugars in the hyphae. In total, hydroxychloroquine disturbed amino acid metabolism, therefore inhibiting the production of biomacromolecules, damaging the cell membrane, and restraining the growth of hyphae, and hence inhibiting gray mold on tomato. This study will explore the use of medicine in the development of agricultural fungicides and their application in managing crop diseases, providing valuable background information.
研究领域:
植物病理学
·
分子生物学
·
农业科学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Zixu Wang,Shanshan Xiang,Yihe Qiu,Fangying Yu,Sufen Li,Shufen Zhang,Guangtao Song,Yichong Xu,Tingting Meng,Hong Yuan,Fuqiang Hu
Cellular iron is inseparably related with the proper functionalities of mitochondria for its potential to readily donate and accept electrons. Though promising, the available endeavors of iron chelation antitumor therapies have tended to be adjuvant therapies. Herein, we conceptualized and fabricated an “iron-phagy” nanoparticle (Dp44mT@HTH) capable of inducing the absolute devastation of mitochondria via inhibiting the autophagy-removal of impaired ones for promoting cancer cell death. The Dp44mT@HTH with hyaluronic acid (HA) as hydrophilic shell can specifically target the highly expressed CD44 receptors on the surface of 4T1 tumor cells. After internalization and lysosomal escape, the nanoparticle disassembles in response to the reactive oxygen species (ROS), subsequently releasing the iron chelator Dp44mT and autophagy-inhibitory drug hydroxychloroquine (HCQ). Dp44mT can then seize cellular Fe 2+ to trigger mitochondrial dysfunction via respiratory chain disturbance, while HCQ not only lessens Fe 2+ intake, but also impedes fusions of autophagosomes and lysosomes. Consequentially, Dp44mT@HTH induces irreversible mitochondrial impairments, in this respect creating a substantial toxic stack state that induces apoptosis and cell death. Initiating from the perspective of endogenous substances, this strategy illuminates the promise of iron depletion therapy via irreversible mitochondrial damage induction for anticancer treatment.
研究领域:
肿瘤学
·
纳米医学
·
细胞生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF POWER SOURCES
·
2023
·
IF 9.2
Chengzhi Wang,Yi Xing,Kangning Zhang,Huizi Zheng,Ya-nan Zhang,Xiaolin Zhu,Xing Yuan,Jiao Qu
A photocathode-microbial electrochemical coupling system (PC-MFC) using black phosphorus-doped titanium dioxide nanobelt (BP/TB) as a photocatalyst is constructed for the degradation of hydroxychloroquine (HCQ, used to treat COVID-19). The degradation efficiency of HCQ (100 mg/L) in coupling system is 73.7% within 8 h, higher than that of photocatalysis (69.5%), MFC (25.6%), and adsorption (9.6%). The photocathode coupling facilitates subsequent bioelectric treatment, resulting in complete degradation of HCQ (100 mg/L) within 96 h in PC-MFC, much higher than in MFC (51.1%). Illumination of PC-MFC significantly increases the cathodic abundance of Pseudomonadales ord. (from 1.83% to 66.30%), accumulates biomass, improves the electrochemical behaviors of photocathode and bioanode , and finally increases the maximum power from 241 to 280 mW/m 2 . The electron transfer pathways depende on nicotinamide adenine dinucleotide dehydrogenase, succinate dehydrogenase and terminal oxidase. The coupled system enhances the dechlorination reduction of HCQ and reduces the biotoxicity of its degradation pathway . PC-MFC represents a new strategy for the treatment and energy recovery of refractory organic compounds in wastewater.
研究领域:
环境科学
·
生物化学
·
微生物学
✓ 已验证
DOI
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2025
·
IF 8.4
Ye Cui-fang,Wu Jia-di,Li Lin-rong,Sun Shu-guo,Wang Yu-gang,Jiang Tian-an,Long Xin,Zhao Jun
Irreversible electroporation (IRE) is a local ablative treatment for patients with pancreatic cancer. During the IRE procedure, high-intensity electric pulses are released intratumorally to disrupt plasma membranes and induce cell death. Since the intensity of the pulsed electric field (PEF) can be decreased by the tumor microenvironment, some cancer cells are subjected to a sublethal PEF and may survive to cause tumor recurrence later. Autophagy activation induced by anticancer therapies is known to promote treatment resistance. In this study, we investigated whether autophagy is activated in residual cancer cells after IRE and assessed the roles it plays during tumor recurrence. Subcutaneous KPC-A548 or Panc02 murine pancreatic cancer cell line xenograft mouse models were established; once the tumors reached 7 mm in one dimension, the tumor-bearing mice were subjected to IRE. For in vitro sublethal PEF treatment, the pancreatic cancer cell suspension was in direct contact with the electrodes and pulsed at room temperature. We showed that autophagy was activated in surviving residual cells, as evidenced by increased expression of LC3 and p62. Suppression of autophagy with hydroxychloroquine (60 mg/kg, daily intraperitoneal injection) markedly increased the efficacy of IRE. We demonstrated that autophagy activation can be attributed to increased expression of high-mobility group box 1 (HMGB1); co-inhibition of two HMGB1 receptors, receptor for advanced glycosylation end products (RAGE) and Toll-like receptor 4 (TLR4), suppressed autophagy activation by upregulating the PI3K/AKT/p70 ribosomal S6 protein kinase (p70S6K) axis and sensitized pancreatic cancer cells to PEF. We prepared a polymeric micelle formulation (M-R/T) encapsulating inhibitors of both RAGE and TLR4. The combination of IRE and M-R/T (equivalent to RAGE inhibitor at 10.4 mg/kg and TLR4 inhibitor at 5.7 mg/kg, intravenous or intraperitoneal injection every other day) significantly promoted tumor apoptosis, suppressed cell cycle progression, and prolonged animal survival in pancreatic tumor models. This study suggests that disruption of HMGB1-mediated autophagy with nanomedicine is a promising strategy to enhance the response of pancreatic cancer to IRE.
研究领域:
肿瘤学
·
癌症生物学
·
分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2024
·
IF 8.5
Yicheng Ren,Quan Ma,Dong Li,Yanpei Chen,Qinyang Cheng,Zisheng Luo
Fluctuations in energy status are critical physiological factors influencing postharvest fruit quality. However, the role of autophagy, a stress-resistant biological process, in regulating postharvest fruit energy status remains unclear. In this study, we treated strawberry fruit with the autophagy inhibitor hydroxychloroquine (HCQ) to investigate the role of autophagy in maintaining energy status. The results demonstrated that HCQ treatment inhibited autophagosome formation, reducing relative autophagic activity by 73 % on day 6. HCQ treatment also reduced the energy charge and the NADH/NAD + ratio by 5 % and 61 %, respectively, on day 2. Corresponding to the decline in energy status, HCQ treatment led to a reduction in cytochrome C oxidase (CCO) and succinate dehydrogenase (SDH) activities by 47.48 % and 56.34 %, respectively, on day 3. Additionally, fluctuations in energy charge led to abnormalities in ripening and decreased stress resistance in autophagy-inhibited fruit. In conclusion, this study provides evidence that autophagy-mediated energy charge sustainability mitigates postharvest quality deterioration in fruit.
研究领域:
植物生理学
·
采后生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
CHEMBIOCHEM
·
2024
·
IF 2.6
Chunyu Yan,Wei Zhou,Yan Zhang,Xuelian Zhou,Qinglong Qiao,Lu Miao,Zhaochao Xu
In this study, super-resolution structured illumination microscope (SIM) was used to analyze molecular mechanism of endocytic acidification inhibitors in the SARS-CoV-2 pandemic, such as Chloroquine (CQ), Hydroxychloroquine (HCQ) and Bafilomycin A1 (BafA1). We fluorescently labeled the SARS-CoV-2 RBD and its receptor ACE2 protein with small molecule dyes. Utilizing SIM imaging, the real-time impact of inhibitors (BafA1, CQ, HCQ, Dynasore) on the RBD-ACE2 endocytotic process was dynamically tracked in living cells. Initially, the protein activity of RBD and ACE2 was ensured after being labeled. And then our findings revealed that these inhibitors could inhibit the internalization and degradation of RBD-ACE2 to varying degrees. Among them, 100 nM BafA1 exhibited the most satisfactory endocytotic inhibition (~63.9%) and protein degradation inhibition (~97.7%). And it could inhibit the fusion between endocytic vesicles in the living cells. Additionally, Dynasore, a widely recognized dynein inhibitor, also demonstrated cell acidification inhibition effects. Together, these inhibitors collectively hinder SARS-CoV-2 infection by inhibiting both the viral internalization and RNA release. The comprehensive evaluation of pharmacological mechanisms through super-resolution fluorescence imaging has laid a crucial theoretical foundation for the development of potential drugs to treat COVID-19.
研究领域:
病毒学
·
细胞生物学
·
药理学
·
成像科学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Natural Medicines
·
2024
·
IF 2.5
Chen Ping,Zhang Xueer,Fang Qiaomiao,Zhao Zhongxiang,Lin Chaozhan,Zhou Yuan,Liu Fangle,Zhu Chenchen,Wu Aizhi
Betulinic acid (BA), a naturally occurring lupane-type triterpenoid, possesses a wide range of potential activities against different types of cancer. However, the molecular mechanisms involved in anti-cervical cancer about BA were rarely investigated. Herein, the role of BA in cervical cancer suppression by ROS-mediated endoplasmic reticulum stress (ERS) and autophagy was deeply discussed. The findings revealed that BA activated Keap1/Nrf2 pathway and triggered mitochondria-dependent apoptosis due to ROS production. Furthermore, BA increased the intracellular Ca 2+ levels, inhibited the expression of Beclin1 and promoted the expression of GRP78, LC3-II, and p62 associated with ERS and autophagy. Besides, BA initiated the formation of autophagosomes and inhibited autophagic flux by the co-administration of BA with 3-methyladenine (3-MA) and chloroquine (CQ), respectively. The in vivo experiment manifested that hydroxychloroquine (HCQ) enhanced the apoptosis induced by BA. For the first time, we demonstrated that BA could initiate early autophagy, inhibit autophagy flux, and induce protective autophagy in HeLa cells. Thus, BA could be a potential chemotherapy drug for cervical cancer, and inhibition of autophagy could enhance the anti-tumor effect of BA. However, the interactions of signaling factors between ERS-mediated and autophagy-mediated apoptosis deserve further attention. Graphical abstract
研究领域:
肿瘤学
·
细胞生物学
·
药理学
✓ 已验证
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）