ANALYST
·
2020
·Vol. 145
·期 24
·8016-8021
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IF 3.978
Qiaoling Liu,Ying Zhao,Yan Zhang,Kaixin Xie,Ruirong Liu,Borong Ren,Yanmei Yan,Lin Li
A turn-on spiropyran functionalized fluorescein derivative (FMC) is developed for targeting HS− in mitochondria. FMC exhibits very weak fluorescence at 525 nm under the excitation of 470 nm in aqueous solution due to its colorless spiropyran form; upon addition of HS−, a strong fluorescence enhancement by 6.4-fold is observed with spirocycle-opened merocyanine form and rapid trapping kinetics for HS−. FMC has good biocompatibility and high selectivity towards HS− with a detection limit of 88.2 nM and is very sensitive among the reported H2S fluorescent probes. Moreover, the significant colocalization of FMC with Mito Tracker® Deep Red FM in human laryngeal epidermoid carcinoma (HEp-2) cells and the Pearson correlation coefficient of 0.87 together demonstrate that FMC can target and image the endogenous H2S in the mitochondria of living cells.
研究领域:
生物化学
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医学影像
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细胞生物学
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DOI
高影响因子
JOURNAL OF ALLOYS AND COMPOUNDS
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2022
·
IF 6.371
Ruiting Zhang,Yahong Jin,Lifang Yuan,Kaiyuan Deng,Chuanlong Wang,Guangting Xiong,Li Chen,Yihua Hu
Photochromic materials usually have different physical and chemical properties when they are in different states. Inorganic photochromic materials are widely used in the fields of information storage, optical switches and sensors due to their long lifetime, good thermal stability and fatigue resistance . However, the current inorganic photochromic materials, possessing a unitary optical property , cannot fulfill the requirement of multimodal high-level security anti-counterfeiting. In this work, we report the multiple optical behaviors integrated inorganic photochromic Er 3+ -doped strontium hafnate ceramics. It integrates multiple optical functions, including photochromism, downshifting photoluminescence , up-conversion luminescence, afterglow, and thermoluminescence . The fluorescence modulation contrast (FMC) maximum of SrHfO 3 : Er 3+ can achieve as high as to 77.21% in the mode of photochromism-driven the quenching of downshifting photoluminescence. The FMC maximum can approach 70.24% in the mode of photochromism-driven the quenching of up-conversion luminescence. By alternating the light stimulation and thermal field effect, both photochromism and fluorescence modulation exhibit excellent stability and robust fatigue resistance. The mechanisms of the observed photochromism, downshifting and up-conversion luminescence, fluorescence modulation, afterglow, and thermoluminescence were studied systematically. The combination of the multiple optical behaviors functionalizes the as-obtained material for versatile applications. As a proof of concept, a flexible film was designed and prepared, demonstrating the practical application of SrHfO 3 : Er 3+ material for multimodal high-level security anti-counterfeiting.
研究领域:
材料科学
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光学
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光子学
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安全与防伪
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DOI
高影响因子
Future Medicinal Chemistry
·
2019
·Vol. 12
·期 2
·
IF 3.617
Dandan Liang,Zhengying Su,Wei Tian,Junying Li,Zhaoquan Li,Chunmiao Wang,Danrong Li,Huaxin Hou
Aim: The EGF receptor (EGFR) is overexpressed in multiple epithelial-derived cancers and is considered to be a vital target closely associated with cancer therapy. In this study, a series of novel anthraquinone−quinazoline hybrids targeting several vital sites for cancer therapy were designed and synthesized. Methodology & results: Most of the synthesized hybrids demonstrated excellent antiproliferative activity and downregulation of the expression of EGFR. The most promising compound 7d showed the strongest antiproliferation activity; this compound significantly downregulated the expression of p-EGFR protein, induced a remarkable apoptosis effect, promoted the rearrangement of F-actin filaments and destruction of cytoskeleton, induced DNA damage and enhanced radiosensitivity of A549 cells. Conclusion: The novel anthraquinone−quinazoline hybrid 7d emerges as an anticancer drug candidate with promising multitargeted biological activities.
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
Future Medicinal Chemistry
·
2017
·Vol. 9
·期 16
·
IF 3.556
Kan Yang,Biao Gao,Xianjun Ming,Zhipeng Huang,Minghui Wang,Jibin Dong,Jinxin Wang
Aim: ASM, which hydrolyzes sphingomyelin into ceramide, is recognized as a therapeutic target for UV-induced skin damage. Direct inhibitors for this enzyme are rare. Here we synthesized several series of 1,3,6,7-tetrahydroxy-xanthone derivatives as novel ASM inhibitors. Results: Several compounds were more potent than the lead compound, among which 5b was found competitively inhibiting the enzyme and dose-dependently reducing ceramide generation. Furthermore, 5b and 5c showed excellent protective effect to skin keratinocytes against UV. Quantitative structure–activity relationship investigation revealed detail relationships between molecular structure and biological activity. Insight into the binding mode was precisely illuminated by molecule docking. Conclusion: This work would provide fresh ideas and strong supports for further development of ASM inhibitors and drug candidates for skin damage.
研究领域:
药理学
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皮肤病学
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化学生物学
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DOI
PubMed
高影响因子
Future Medicinal Chemistry
·
2021
·Vol. 13
·期 13
·
IF 3.808
Xin Lu,Yijun Liu,Nan Qin,Hongyu Yang,Yuting Qiao,Xueyang Jiang,Yao Chen,Feng Feng,Wenyuan Liu,You Zhou,Haopeng Sun
Background: Alzheimer's disease is a multifactorial neurological disorder seen in elderly people. Loss of cholinergic transmission and unbalanced tryptophan metabolism kynurenine pathway have been demonstrated in neuropsychiatric diseases. Methods & results: Among the two series of synthesized compounds, compounds 5c and 5h were identified as effective dual BChE/IDO1 inhibitors, with well-balanced micromolar activity. Compounds 5c and 5h exhibited promising ability to ameliorate behavioral impairment by Morris water maze. The safety of miconazole analogs was also validated by PC12 and SH-SY5Y cell lines. Conclusion: These results highlight the ability of 5c and 5h to treat Alzheimer's disease.
研究领域:
神经科学
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药物化学
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老年医学
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DOI
PubMed
高影响因子
Future Medicinal Chemistry
·
2022
·Vol. 14
·期 20
·
IF 4.767
Haijun Gu,Ting Zhang,Yunqi Li,Yuan He,Tian Guan,Weiqiong Kan,Peng He,Zhengfang Yi,Yihua Chen
Aim: The first inhibitor targeting myoferlin (MYOF), WJ460, bears poor metabolic stability and water solubility. Therefore, this study aimed to improve the drug-like properties of WJ460. Materials & methods: The authors synthesized an array of 1,5-diaryl-1,2,4-triazole analogs and appraised the binding activities with MYOF and their antiproliferative and antimigratory activities against pancreatic cancer cells. Results: Molecular docking and surface plasmon resonance results showed that E4 was directly bound to the MYOF-C2D domain. E4 effectively inhibited the proliferation and migration of pancreatic cancer cells in vitro. An in silico study suggested that the water solubility of E4 was improved by about 22-times than that of WJ460. Conclusion: The findings suggested that the druglike ability of E4 was significantly improved.Graphical abstract
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
Future Medicinal Chemistry
·
2023
·
IF 4.2
Li Zhu,Xiujin Chang,Shengpeng Zhang,Xiumei Bai,Alexander V Finko,Xi Xu,Jinlei Bian,Xiaoping Liu,Huidan Huang
Aim: A series of novel GLS1 irreversible allosteric inhibitors targeting Lys320 might have robust enzyme inhibitory activity and potent antitumor activity. Materials & methods: Novel GLS1 allosteric inhibitors targeting Lys320 were synthesized and their anticancer activity was assessed. Moreover, GLS1 protein was used as a model system to analyze the reactivity of these electrophilic groups in GLS1 irreversible allosteric inhibitors with other amino acids, including tyrosine, histidine, serine and threonine, using biochemical and biophysical assays. Results: AC16 exhibited robust GLS1 inhibitory activity, antiproliferative effect in vitro, good plasma stability and potential covalent addition with GLS1 K320. Conclusion: This study opens a novel avenue for the design of robust irreversible GLS1 inhibitors targeting the allosteric site K320.Graphical abstract
研究领域:
癌症研究
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分子生物学
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药理学
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DOI
PubMed
高影响因子
Future Medicinal Chemistry
·
2021
·Vol. 13
·期 11
·
IF 3.808
Baowei Yang,Yicheng Mei,Qianhui Li,Mengyuan Zhang,Huiling Tang,Tong Liu,Feng Feng,Qiyun Fu,Yuzhang Jiang,Qizhuang Ye
There is an urgent need for new antibiotics and alternative strategies to combat bacterial pathogens. Molecular docking, antibacterial evaluation in vitro and in vivo, cytotoxicity assessment and enzyme inhibition analyses were performed. Compound 12 exhibited antimicrobial activity against Staphylococcus aureus (MIC: 4 μg/ml), various clinically isolated strains of MRSA (MIC: 4–16 μg/ml) and Acinetobacter baumannii (MIC: 4 μg/ml) when combined with subinhibitory concentrations of colistin B. Compound 12 (20 mg/kg) yielded mild improvement in survival of methicillin-resistant Staphylococcus aureus (MRSA)-infected mice. Additionally, enzyme inhibition tests showed that compound 12 exhibited inhibitory effects against S. aureus dihydrofolate reductase (105.1 μg/ml) and DNA gyrase (122.8 μg/ml). Compound 12 is a promising antibacterial candidate for further development.Graphical abstractCelecoxib analogue 12 possesses considerable antibacterial activity in vivo and in vitro and is relatively safe, making it a promising lead for further optimization as an antibacterial therapeutic agent.
研究领域:
药理学
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微生物学
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医学
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DOI
PubMed
高影响因子
Future Medicinal Chemistry
·
2023
·Vol. 15
·期 2
·
IF 4.2
Honglan Zhai,Chunmiao Wang,Junying Li,Dandan Liang,Fengming Li,Qiuping Zhang,Jingni Wang,Tuo Ma,Danrong Li,Huaxin Hou
Background: Endoplasmic reticulum (ER) stress is a therapeutic target in cancer given its regulation of bioenergetics and cell death. Methodology & results: We synthesized 14 ER stress-triggered anthraquinone derivatives by introducing an amino group at the 3-position side chain of the lead compound obtained previously. Most of the anthraquinone derivatives exhibited good antitumor activity due to their ability to induce ER damage through cytoplasmic vacuoles. The mechanisms of ER stress caused by compound KA-4c were related to increasing the expression levels of the ATF6 and Bip proteins and upregulating CHOP and cleaved PARP. Conclusion: Compound KA-4c triggers ER stress response and induces apoptosis via the ATF6–CHOP signaling pathway.Graphical abstract
研究领域:
肿瘤学
·
细胞生物学
·
药物化学
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DOI
PubMed
高影响因子
Future Medicinal Chemistry
·
2019
·Vol. 11
·期 10
·
IF 3.617
Xi-Hui Yu,Xiong-Jie Cai,Xiao-Qiao Hong,Kin Yip Tam,Kun Zhang,Wen-Hua Chen
Aim: Anion/cation symport across cellular membranes may lead to cell apoptosis and be developed as a strategy for new anticancer drug discovery. Methodology: Four aza-crown ether–squaramide conjugates were synthesized and characterized. Their anion recognition, anion/cation symport, cytotoxicity and probable mechanism of action were investigated in details. Conclusion: These conjugates are able to form ion-pairing complexes with chloride anions and facilitate the transmembrane transport of anions via an anion/cation symport process. They can disrupt the cellular homeostasis of chloride anions and sodium cations and induce the basification of acidic organelles in live cells. These conjugates exhibit moderate cytotoxicity toward the tested cancer cells and trigger cell apoptosis by mediating the influx of chloride anions and sodium cations into live cells. Graphical abstract
研究领域:
药理学
·
生物化学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
Future Medicinal Chemistry
·
2019
·Vol. 11
·期 20
·
IF 3.617
Hongmei Xu,Fangfang Teng,Feilong Zhou,Li Zhu,Yi Wen,Runliang Feng,Zhimei Song
Aim: To encapsulate amphotericin B (AmB) with reduced toxicity and comparable activity. Results & methodology: The α-linolenic acid (ALA)-modified monomethoxy polyethylene glycol-g-PEI-g-ALA conjugate was employed to prepare AmB-loaded micelles (AmB-M). In vitro activity and release behavior of AmB-M were investigated. AmB-M enhanced AmB's water-solubility to 1.2 mg/ml, showing good storage stability. AmB-M could achieve a sustained and slow release of AmB, low hemolysis activity and negligible kidney toxicity when compared with commercial AmB injection. Antifungal activity and biofilm inhibition experiments confirmed that the antifungal activity of AmB-M against Candida albicans was similar to that of AmB injection. Conclusion: Monomethoxy polyethylene glycol-g-PEI-g-ALA micelles could be a preferable choice to treat systemic fungal infections as an efficient drug delivery system.
研究领域:
药剂学
·
抗感染研究
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产品关联
DOI
PubMed
高影响因子
Future Medicinal Chemistry
·
2021
·Vol. 13
·期 15
·
IF 3.808
Yunong Li,Jingbo Yang,Yan Zhang,Qingkang Meng,Andreas Bender,Xiujie Chen
Background: A comprehensive approach to drug repositioning will be required to overcome translational hurdles and identify more neuroprotective drugs. Results & methods: Gene Set Enrichment Analysis was applied to identify related pathways and enriched genes. Candidate genes were optimized using ToppGene, ToppGenet and pBRIT. From the perspective of the local structures, gene–domain–substructure–drug relationships were constructed. Using the MCODE algorithm and K-means clustering, 31 functional subnetworks were obtained, and 252 drugs with proposed neuroprotective function were identified. Using computational analysis, 72 substructures with different scores were found to correspond to neuroprotective functions. The protective effects of benidipine and barnidipine were confirmed in vitro. Conclusion: The authors' research has great potential to discover more neuroprotective drugs and obtain more information regarding mechanisms of action and functional substructures.
研究领域:
生物信息学
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药物研发
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神经科学
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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）