Frontiers in Pharmacology
·
2023
·
IF 5.6
Chen Lexian,Lv Qianqian,Cai Jianghong,Liang Jiajie,Liang Ziyan,Lin Jiahui,Xiao Ying,Chen Ruiyao,Zhang Zhiling,Hong Yue,Ji Hong
Coumarin derivatives have diverse structures and show various significant biological activities. Aiming to develop more potent coumarin derivatives for cancer treatment, a series of coumarin acrolein hybrids were designed and synthesized by using molecular hybridization approach, and investigated for their antiproliferative activity against A549, KB, Hela and MCF-7 cancer cells as well as HUVEC and LO2 human normal cells. The results indicated that most of the synthesized compounds displayed remarkable inhibitory activity towards cancer cells but low cytotoxicity on normal cells. Among all the compounds, 5d and 6e were the most promising compounds against different cancer cell lines, especially for A549 and KB cells. The preliminary action mechanism studies suggested that compound 6e, the representative compound, was capable of dose-dependently suppressing migration, invasion and inducing significant apoptosis. Furthermore, the combined results of network pharmacology and validation experiments revealed that compound 6e induced mitochondria dependent apoptosis via the PI3K/AKT-mediated Bcl-2 signaling pathway. In summary, our study indicated compound 6e could inhibit cell proliferation, migration, invasion and promote cell apoptosis through inhibition of PI3K/AKT signaling pathway in human oral epidermoid carcinoma cells. These findings demonstrated the potential of 3-(coumarin-3-yl)-acrolein derivatives as novel anticancer chemotherapeutic candidates, providing ideas for further development of drugs for clinical use.
研究领域:
药理学
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肿瘤学
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化学
·
细胞生物学
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DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2023
·
IF 5
Pingfu Huang,Hui Yan,Hao Wu,Lulu Liu,Wenmin Niu,Bo Zhai,Ziwei Hu,Jingjuan Li,Qianming Du,Yang Zhou
The co-amorphous (CAM) system has attracted widely attention for improving the solubility of poor water solubility drug and provide a formulation strategy for combination administration system. Paclitaxel (PTX) belongs to biopharmaceutics classification system (BCS) class Ⅳ drug, with the poor water solubility and membrane permeability. This study aimed to preparing the CAM system between PTX and curcumin (CUR) by rotary evaporation method. The solid-state characterization of CAM indicated that the PTX and CUR presented as amorphous state, compared with crystalline PTX and CUR, the amorphous system could improve the saturated solubility and dissolution with significantly difference, besides, the PTX absorption permeability increased after amorphization with CUR, and the rat pharmacokinetic study exhibited that the PTX-CUR had a high C max and AUC 0-∞ compared with crystalline CUR and PTX, Furthermore, the amorphous CUR and PTX exhibited the stronger anti-tumor efficacy in A549 cell model in vivo . In addition, PTX-CUR exhibited physical stability under the long-term storage condition. In conclusion, amorphization of PTX and CUR provided a promising mothed to improve the anti-tumor efficacy and oral bioavailability of PTX.
研究领域:
药学
·
药理学
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药物递送系统
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肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Tongmei Shi,Jieling Lin,Shiyun Liang,Yu Song,Xin Zhao,Mengjie Xiao,Huihui Ti
A B S T R A C T Headings ethnopharmacological relevance Sangbaipi Decoction (SBPD) is an effective treatment for lung diseases caused by phlegm-heat obstruction according to Jingyue Quanshu , and soothes panting by purging the lung meridian. It is composed of anti-pyretic herbs (e.g., Scutellaria baicalensis Georgi and Coptis chinensis Franch.) and antitussive herbs (e.g., Cortex Mori and Armeniacae Semen Amarum ). Therefore, we hypothesized that SBPD has therapeutic effects on lung injury caused by influenza virus. Aim of the study This study aimed to explore anti-influenza activity, active components, and mechanisms of SBPD. Materials and methods The anti-influenza activities of SBPD were determined in 48 h drug-treated MDCK cell model using CPE and plaque reduction assays, and 24 h drug-treated A549 cells using qRT-PCR. The in vivo efficacy of SBPD (1.0g/kg/day and 0.5g/kg/day) was evaluated in PR8 infected BALB/c mice. The chemical component was assessed through HPLC-Q-TOF MS/MS analysis. Network pharmacology was built via TCMSP, GeneCards, DisgeNet, OMIM, DrugBank databases, and Cytoscape software. Additionally, TOA, HI and NAI assays were employed to investigate impact on the virus replication cycle with different concentrations of SBPD (2.5 mg/mL, 1.25 mg/mL, or 0.625 mg/mL). Results In MDCK infected with viruses A/PR/8/34, A/Hong Kong/1/68, or A/California/4/2009, the IC 50 values of SBPD were 0.80 mg/mL, 1.20 mg/mL, and 1.25 mg/mL. In A549 cells, SBPD treatment reduced cytokine expression (e.g., TNF-α, IL-6, IL-1β) ( p < 0.05). In PR8 infected BALB/c mice, SBPD improved the survival rate of infected mice, reduced lung index ( p < 0.05), protected lung tissue from pathological damage, and regulated cytokine overexpression ( p < 0.05). 29 components of SBPD were identified in SBPD treated mouse serum including some phytochemicals targeting influenza proteins. HI and NAI assays suggested the potential antiviral mechanism of SBPD through inhibition of HA and NA. Conclusion This study is the first to demonstrate the anti-influenza and the anti-inflammatory effects of SBPD in vitro and in vivo. Its major anti-influenza phytochemicals were explored and its inhibitory effects on HA and NA protein were proved. It provides more options for anti-influenza drug discovery.
研究领域:
药理学
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病毒学
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中医
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TETRAHEDRON
·
2018
·
IF 2.377
Yuliang Jiang,Sheng Zhang,Bingxiang Wang,Tao Qian,Can Jin,Shishan Wu,Jian Shen
Hypochlorite (OCl − ) plays important roles both in physiological and pathological processes, the detection of which is of great significance. Herein, a novel fluorescent probe based on the triphenylamine-type schiff base derivative (TPAD) was developed to detect OCl − . Probe TPAD exhibited specific fluorescence response toward ClO − with the fluorescence quenching rate up to 80%, and the detection limit was estimated to be 0.8 μM. The sensing mechanism study demonstrated that TPAD reacted with ClO − via an oxidation process, which was evidenced by MS and NMR characterization. Moreover, owing to the excellent sensing properties and negligible cytotoxicity, TPAD was successfully applied in the bioimaging of OCl − in living A549 cells.
研究领域:
分析化学
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生物化学
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生物医学工程
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细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2022
·Vol. 46
·期 46
·22441-22450
·
IF 3.925
Xiaona Zhu,Zegao Wang,Jing Hu,Zhengcheng Lu,Mingyan Gao,Ying Wang,Zhengxun Song,Mingdong Dong,Zuobin Wang,Lasse Hyldgaard Klausen
Cell viability detection plays a crucial role in apoptosis and anticancer drug research. Compared with conventional colorimetric assays and organic fluorescent probe-based imaging, it is greatly desired to develop a simple and facile fluorescent probe for in situ real-time detection of cell viability. Herein, MoS2 nanoflakes are employed as fluorescent probes for detecting cancer cell viability by using their inherent tunable photoluminescence (PL) properties by ion intercalation. The appropriate amount of MoS2 nanoflakes for A549 lung cancer cells was firstly determined by MTT assay. After MoS2 nanoflakes successfully covered cells, the effects of the nanoflakes on cell morphology and mechanical properties were studied by atomic force microscopy (AFM). Then, the modulation of PL by potassium ions (K+) from cells was investigated at different cell viabilities. The results showed that PL intensity increased as cell viability decreased. Finally, the nanoflakes were further used as fluorescent probes to assess the cell viability change induced by anticancer drugs. The results showed that with the increase of drug concentration, the fluorescence intensity increased, indicating a decrease in cell viability. The ion-modulated PL of MoS2 nanoflakes makes MoS2 a promising candidate for applications in anticancer drug screening.
研究领域:
生物材料
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纳米技术
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癌症研究
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生物物理学
✓ 已验证
产品关联
DOI
高影响因子
ACS Omega
·
2024
·
IF 3.7
Tengjiao Fan,Lin Shen,Yaxin Huang,Xin Wang,Lijiao Zhao,Rugang Zhong,Peng Wang,Guohui Sun
Lung cancer ranks as the second most diagnosed cancer and the leading cause of cancer-related deaths worldwide. Novel chemotherapeutic strategies are crucial to efficiently target tumor cells while minimizing toxicity to normal cells. In this study, we proposed a combination strategy using energy blocker lonidamine (LND) and cytotoxic drug nimustine (ACNU, 1-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-3-(2-chloroethyl)-3-nitrosourea) to enhance the killing of a human lung cancer cell line and investigated the potential chemo-sensitizing mechanism of LND. LND was found to remarkably increase the cytotoxicity of ACNU to A549 and H1299 cells without significantly affecting normal lung BEAS2B cells. The combination of LND and ACNU also produced significant effects on cell apoptosis, colony formation, cell migration, and invasion assays compared to single drug treatment. Mechanistically, LND decreased intracellular ATP levels by inhibiting glycolysis and inducing mitochondrial dysfunction. Furthermore, the combination of LND and ACNU could intensify cellular oxidative stress, decrease cellular GSH contents, and increase reactive oxygen species (ROS) production. Notably, LND alone dramatically downregulated the expression of DNA repair protein MGMT (O6-methylguanine-DNA methyltransferase), enhancing DNA interstrand cross-link formation induced by ACNU. Overall, LND represents a potential chemo-sensitizer to enhance ACNU therapy through energy inhibition, disrupting redox homeostasis and downregulating MGMT expression in human lung cancer cell line under preclinical and clinical background.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
·
2019
·
IF 3.31
Yun Li,Yueqin Li,Nana Wang,Dong Lin,Xiaohui Liu,Yong Yang,Qinwei Gao
Two new nickel (II) triphenylphosphine complexes derived from tridentate aroylhydrazone ligands [H2L1 = 2-hydroxy-3-methoxybenzylidene)benzohydrazone and H2L2 = N′-(2-hydroxy-3-methoxybenzylidene)-2-hydroxybenzoylhydrazone] and triphenylphosphine were prepared and their molecular structures were determined by single crystal X-ray diffraction analysis. Both nickel(II) complexes showed slightly distorted square planar geometry with one tridentate aroylhydrazone ligand coordinated through ONO donor atoms and one triphenylphosphine ligand coordinated to the nickel center through the phosphorus atom. DNA interaction studies indicated that both complexes possessed higher affinity to herring sperm DNA (HS-DNA) than the corresponding free aroylhydrazone ligand. Molecular docking investigations showed that both complexes could bind to DNA through intercalation of the phenyl rings between adjacent base pairs in the double helix. Meanwhile, bovine serum albumin (BSA) binding studies revealed the complexes could effectively interact with BSA and change the secondary structure of BSA. Further pharmacological evaluations of the synthesized complexes by in vitro antioxidant assays demonstrated high antioxidant activity against NO· and O2˙− radicals. The anticancer activity of each complex was assessed through in vitro cytotoxicity assays (CCK-8 kit) toward A549 and MCF-7 cancer cell and normal L-02 cell lines. Significantly, the Ni(II) complex derived from H2L1 ligand was found to be more effective cytotoxic toward MCF-7cancerous cell with the IC50 value equaled 9.7 μM, which showed potent cytotoxic activity over standard drug cisplatin. AbbreviationsA549human lung carcinoma cellBSAbovine serum albuminCCK-8Cell Counting Kit-8DFTdensity functional theoryDNAdeoxyribonucleic acidDPPH˙2,2-diphenyl-1-picrylhydrazylH2L12-hydroxy-3-methoxybenzylidene)benzohydrazone N′-(2-hydroxy-3-methoxybenzylidene)-2-hydroxybenzoylhydrazoneH2L2N′-(2-hydroxy-3-methoxybenzylidene)-2-hydroxybenzoylhydrazoneHOMOhighest occupied molecular orbitalIC50the 50% activityL-02human normal liver cellLOMOlowest unoccupied molecular orbital (LUMO)MCF-7human breast carcinoma cellNO˙nitric oxideO2˙−superoxide anionSODsuperoxide dismutaseCommunicated by Ramaswamy H. Sarma
研究领域:
无机化学
·
生物化学
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药理学
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癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2021
·
IF 6.953
Xin Gang,Lu Wang,Jianhong Jia,Huifang Wang,Xiaojie Lian,Xianghua Gao,Baolong Niu,Wenfeng Li
Cancer is becoming a major threat to national public health security. The integration of disease diagnosis and monitoring with treatment has become a hot spot for researchers. The amorphous calcium phosphate (ACP) nanoparticles prepared by the group in the previous stage could not precisely treat the lesion without tumor targeting and imaging characteristics. In this paper, water-soluble hyaluronic acid fluorescent carbon nanoparticles (HA-FCNs) were prepared and co-interacting with ACP nanoparticles to form hyaluronic acid fluorescent carbon/amorphous calcium phosphate (HA-FCNs/ACP) nanoparticles. The basic characteristics were characterized and the biological characteristics before and after drug loading were evaluated. HA-FCNs/ACP nanoparticles have good hemocompatibility, pH responsiveness, and enzymatic release. HA-FCNs and HA-FCNs/ACP nanoparticles are dispersed in the cytoplasm through the overexpressed CD44 receptors, which are actively targeted into A549 cells. Besides, the migration of A549 cells would be inhibited after cells were treated with drug-loaded nanomaterials. Therefore, the as-prepared nanoparticles can be used to monitor and treat focal sites through tumor-targeting bioimaging, pH-responsive, and enzymatic drug release properties, thus enabling integrated diagnosis and treatment.
研究领域:
纳米技术
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生物医学工程
·
药学
·
癌症研究
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生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2017
·
IF 4.811
Yangjian Chen,Fujun Peng,Xiaoda Song,Jicheng Wu,Wenbin Yao,Xiangdong Gao
Polymer-based paclitaxel (PTX) conjugates have demonstrated application potentials to improve the water solubility and enhance the efficiency of drug delivery. In this study, a novel HA-based drug conjugate, HA-6-PTX, was designed and successfully synthesized by chemically grafting PTX to the C-6 position of N -acetyl- d -glucosamine (GlcNAc) of hyaluronic acid (HA) using hexanediamine as the linker. Leaving the carboxylate of HA chain unaffected, the conjugate with drug loading as high as 21.8% showed an excellent water solubility of 168 mg/mL and exhibited increased drug release in the presence of hyaluronidase. Compared to free PTX, HA-6-PTX demonstrated increased cytotoxicity and enhanced apoptosis-inducing effect against HepG2 and A549 cells due to the increased cellular uptake of drug via HA-receptor mediated endocytosis. It was concluded that the HA-6-PTX conjugate could be potentially utilized for further exploration as targeted drug delivery to enhance antitumor efficacy.
研究领域:
药学
·
癌症研究
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMAZIE
·
2012
·Vol. 67
·期 5
·426-431
·
IF 1.006
Sun Xiaoyi,Chen Jinliang,Chen Hailiang,Liang Wenquan
The transfection agent polycation polyethylenimine (PEI) has been rarely used to construct liposomes for chemical antitumor drugs. In this study, it was introduced into cisplatin (CDDP) encapsulated neutral liposomes (CDDP-NL) by amphiphilic PEI-cholesterol (PEI-Chol) to investigate
its effect on the antitumor activity in A549 cells. The IC50 was 0.65 ± 0.02, 2.94 ± 0.21 and 2.03 ± 0.15 g/ml for CDDP-cationic liposomes (CDDP-CL), CDDP-NL and free CDDP, respectively. The enhanced anticancer activity was attributed to the addition of PEI-Chol
which influenced cellular processing of CDDP. With the help of inhibitors, we found that besides clathrin dependent and actin dependent uptake pathways, caveolae-mediated endocytosis was involved in the internalization of CDDP-CL. Improved internalization of CDDP was observed. Intracellular
Pt accumulations were 6.5 times and 3 times of those in CDDP-NL and free CDDP groups, respectively. The differences of intracellular location caused by endocytosis routes and lysosomes escape capacity of PEI-Chol was observed by fluorescence colocalization studies. PEI-Chol also decreased
the Pt fraction exported out of cells and extended the cellular Pt retention of CDDP liposomes. In conclusion, cationic modification of liposomes with PEI is a potential and promising way for antitumor drug delivery.
研究领域:
药理学
·
肿瘤学
·
药物递送系统
·
细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2017
·
IF 3.756
Yue Yang,Xiaoyu Lu,Qi Liu,Yu Dai,Xiaojie Zhu,Yanli Wen,Jiaqiu Xu,Yang Lu,Di Zhao,Xijing Chen,Ning Li
Combination therapy with two drugs and nanoparticle-based drug delivery systems are widely applied to reduce the adverse effects of traditional treatment by chemotherapeutic drugs. Palmitoyl ascorbate (PA) as a lipophilic derivative of ascorbic acid shows the advantages in cancer treatment. The aim of the study was to prepare a doxorubicin (DOX) and PA co-loaded liposome to synergistically treat tumor and effectively alleviate the toxicity caused by DOX. The effects were evaluated by in vitro and in vivo studies. The liposomes (weight ratio of DOX to PA = 1:20, DOX 1 /PA 20 -LPs) exhibited the strongest synergistic effects, combination index was 0.38, 0.56, and 0.05 in MCF-7, HepG2, and A549 cells, respectively. In vitro cellular uptake study, the intercellular concentration of DOX in DOX 1 /PA 20 -LPs was 2.5-fold greater than DOX loaded liposome, and DOX 1 /PA 20 -LPs was taken in not only by macropinocytosis, but also by clathrin-mediated endocytosis. Intracellular distribution experiment showed that DOX 1 /PA 20 -LPs efficiently concentrated in the nucleus. In vivo studies indicated that co-encapsulated liposome not only showed the strongest antitumor ability by tumor growth suppression, but also significantly enhanced the safety by the change of body weight and reduced damages to other tissues (evidenced by histopathology study). These results indicated that DOX and PA co-delivery liposome successfully enhanced the anticancer efficacy and mitigated the toxicities of DOX, which displayed potential for clinical application with enhanced safety and efficacy.
研究领域:
药理学
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肿瘤学
·
纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Chemistry
·
2024
·
IF 3.8
Xu Xuemei,Zhu Zhaojingtao,Chen Siyu,Fu Yanneng,Zhang Jinxia,Guo Yangyang,Xu Zhouyang,Xi Yingying,Wang Xuebao,Ye Faqing,Chen Huijun,Yang Xiaojiao
Introduction: Cancer, a significant global health concern, necessitates innovative treatments. The pivotal role of chronic inflammation in cancer development underscores the urgency for novel therapeutic strategies. Benzothiazole derivatives exhibit promise due to their distinctive structures and broad spectrum of biological effects. This study aims to explore new anti-tumor small molecule drugs that simultaneously anti-inflammatory and anticancer based on the advantages of benzothiazole frameworks.Methods: The compounds were characterized by nuclear magnetic resonance (NMR), liquid chromatograph-mass spectrometer (LC-MS) and high performance liquid chromatography (HPLC) for structure as well as purity and other related physicochemical properties. The effects of the compounds on the proliferation of human epidermoid carcinoma cell line (A431) and human non-small cell lung cancer cell lines (A549, H1299) were evaluated by MTT method. The effect of compounds on the expression levels of inflammatory factors IL-6 and TNF-α in mouse monocyte macrophages (RAW264.7) was assessed using enzyme-linked immunosorbent assay (ELISA). The effect of compounds on apoptosis and cell cycle of A431 and A549 cells was evaluated by flow cytometry. The effect of compounds on A431 and A549 cell migration was evaluated by scratch wound healing assay. The effect of compounds on protein expression levels in A431 and A549 cells was assessed by Western Blot assay. The physicochemical parameters, pharmacokinetic properties, toxicity and drug similarity of the active compound were predicted using Swiss ADME and admetSAR web servers.Results: Twenty-five novel benzothiazole compounds were designed and synthesized, with their structures confirmed through spectrogram verification. The active compound 6-chloro-N-(4-nitrobenzyl) benzo[d] thiazol-2-amine (compound B7) was screened through a series of bioactivity assessments, which significantly inhibited the proliferation of A431, A549 and H1299 cancer cells, decreased the activity of IL-6 and TNF-α, and hindered cell migration. In addition, at concentrations of 1, 2, and 4 μM, B7 exhibited apoptosis-promoting and cell cycle-arresting effects similar to those of the lead compound 7-chloro-N-(2, 6-dichlorophenyl) benzo[d] thiazole-2-amine (compound 4i). Western blot analysis confirmed that B7 inhibited both AKT and ERK signaling pathways in A431 and A549 cells. The prediction results of ADMET indicated that B7 had good drug properties.Discussion: This study has innovatively developed a series of benzothiazole derivatives, with a focus on compound B7 due to its notable dual anticancer and anti-inflammatory activities. B7 stands out for its ability to significantly reduce cancer cell proliferation in A431, A549, and H1299 cell lines and lower the levels of inflammatory cytokines IL-6 and TNF-α. These results position B7B7 as a promising candidate for dual-action cancer therapy. The study’s mechanistic exploration, highlighting B7’s simultaneous inhibition of the AKT and ERK pathways, offers a novel strategy for addressing both the survival mechanisms of tumor cells and the inflammatory milieu facilitating cancer progression.
研究领域:
药理学
·
肿瘤学
·
药物化学
·
细胞生物学
·
炎症
✓ 已验证
DOI
PubMed
高影响因子
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