CHEMISTRY & BIODIVERSITY
·
2020
·Vol. 17
·期 9
·e2000066
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IF 2.039
Zhiguo Mang,Shuai Zhang,Jing Bai,Meijuan Li,Hao Li
Structural simplification and modification of natural products are always very important resources to antitumor drugs. By introducing various aminomethyl groups and amide groups into the phenanthrene ring of tylophorine, a novel series of tylophorine derivatives have been designed and synthesized, and their antiproliferative activities against MCF-7, A549 and HepG-2 cells have been evaluated, too. The results indicated that most of the prepared compounds exhibited good antitumor activities. Especially, one compound with an {ethyl[2-(morpholin-4-yl)ethyl]amino}methyl group at the side chain exhibited the most significant cytotoxic effects.
研究领域:
肿瘤学
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药物化学
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天然产物研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2017
·
IF 4.233
Xian Li,Yue Yan,Yuanzhe Lin,Jian Jiao,Da Wang,Donghua Di,Ying Zhang,Tongying Jiang,Qinfu Zhao,Siling Wang
In this study, hollow mesoporous carbon nanoparticles (HMCN) and mesoporous carbon nanoparticles (MCN) were used as near-infrared region (NIR) nanomaterials and drug nanocarriers were prepared using different methods. A comparison between HMCN and MCN was performed with regard to the NIR-induced photothermal effect and drug loading efficiency. The results of NIR-induced photothermal effect test demonstrated that HMCN-COOH had a better photothermal conversion efficacy than MCN-COOH. Given the prominent photothermal effect of HMCN-COOH in vitro , the chemotherapeutic drug DOX was chosen as a model drug to further evaluate the drug loading efficiencies and NIR-triggered drug release behaviors of the nanocarriers. The drug loading efficiency of DOX/HMCN-COOH was found to be up to 76.9%, which was higher than that of DOX/MCN-COOH. In addition, the use of an 808 nm NIR laser markedly increased the release of DOX from both carbon carriers in pH 5.0 PBS and pH 7.4 PBS. Cellular photothermal tests involving A549 cells demonstrated that HMCN-COOH had a much higher photothermal efficacy than MCN-COOH. Cell viability experiments and flow cytometry were performed to evaluate the therapeutic effect of DOX/HMCN-COOH and the results obtained demonstrated that DOX/HMCN-COOH had a synergistic therapeutic effect in cancer treatment involving a combination of chemotherapy and photothermal therapy.
研究领域:
材料科学
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纳米技术
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癌症治疗
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Jiahui Ye,Longfei Mao,Luoyijun Xie,Rongjun Zhang,Yulin Liu,Lizeng Peng,Jianxue Yang,Qingjiao Li,Miaomiao Yuan
Chemotherapy is the most common clinical treatment for non-small cell lung cancer (NSCLC), but low efficiency and high toxicity of current chemotherapy drugs limit their clinical application. Therefore, it is urgent to develop hypotoxic and efficient chemotherapy drugs. Theophylline, a natural compound, is safe and easy to get, and it can be used as a modified scaffold structure and hold huge potential for developing safe and efficient antitumor drugs. Herein, we linked theophylline with different azide compounds to synthesize a new type of 1,2,3-triazole ring-containing theophylline derivatives. We found that some theophylline1,2,3-triazole compounds showed a good tumor-suppressive efficacy. Especially, derivative d17 showed strong antiproliferative activity against a variety of cancer cells in vitro, including H460, A549, A2780, LOVO, MB-231, MCF-7, OVCAR3, SW480, and PC-9. It is worth noting that the two NSCLC cell lines H460 H and A549 are sensitive to compound d17 particularly, with IC50 of 5.929 ± 0.97 μM and 6.76 ± 0.25 μM, respectively. Compound d17 can significantly induce cell apoptosis by increasing the ratio of apoptotic protein Bax/Bcl-2 by downregulating the expression of phosphorylated Akt protein, and it has little toxicity to normal hepatocyte cells LO2 at therapeutic concentrations. These data indicate that these theophylline acetic acid-1,2,3-triazole derivatives may be potential drug candidates for anti-NSCLC and are worthy of further study.
研究领域:
肿瘤学
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药物化学
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药理学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Nutrition
·
2022
·
IF 6.59
Xiaoxiao Xu,Chuang Ma,Hang Wu,Yuanqiao Ma,Zejin Liu,Peijie Zhong,Chaolei Jin,Wenjuan Ning,Xiao Wu,Yijie Zhang,Jichang Han,Junpeng Wang
Fructose is a commonly used food additive and has many adverse effects on human health, but it is unclear whether fructose impacts pulmonary fibrosis. TGF-β1, a potent fibrotic inducer, is produced as latent complexes by various cells, including alveolar epithelial cells, macrophages, and fibroblasts, and must be activated by many factors such as reactive oxygen species (ROS). This study explored the impact of fructose on pulmonary fibrotic phenotype and epithelial-mesenchymal transition (EMT) using lung epithelial cells (A549 or BEAS-2B) and the underlying mechanisms. Fructose promoted the cell viability of lung epithelial cells, while N-Acetyl-l-cysteine (NAC) inhibited such. Co-treatment of fructose and latent TGF-β1 could induce the fibrosis phenotype and the epithelial-mesenchymal transition (EMT)-related protein expression, increasing lung epithelial cell migration and invasion. Mechanism analysis shows that fructose dose-dependently promoted the production of total and mitochondrial ROS in A549 cells, while NAC eliminated this promotion. Notably, post-administration with NAC or SB431542 (a potent TGF-β type I receptor inhibitor) inhibited fibrosis phenotype and EMT process of lung epithelial cells co-treated with fructose and latent TGF-β1. Finally, the fibrosis phenotype and EMT-related protein expression of lung epithelial cells were mediated by the ROS-activated latent TGF-β1/Smad3 signal. This study revealed that high fructose promoted the fibrotic phenotype of human lung epithelial cells by up-regulating oxidative stress, which enabled the latent form of TGF-β1 into activated TGF-β1, which provides help and reference for the diet adjustment of healthy people and patients with fibrosis.
研究领域:
肺科学
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细胞生物学
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHINESE JOURNAL OF CHEMICAL ENGINEERING
·
2021
·
IF 3.171
Baolong Niu,Min Li,Jianhong Jia,Lixuan Ren,Xin Gang,Bin Nie,Yanying Fan,Xiaojie Lian,Wenfeng Li
Recently, multifunctional nanoparticles have shown great prospects in cancer treatment, which have the ability to simultaneously deliver the drug, image and target tumor cells. In this paper, we designed a luminescent nanoparticles platform based on hydrothermal hyaluronic acid/amorphous calcium phosphate (HA-FCNs/ACP) with multifunctional properties for drug delivery, bio-imaging, and targeting treatment. HA-FCNs/ACP shows an ability to load curcumin (Cur) with pH-sensitive responsive drug release behavior and excellent biocompatibility. HA-FCNs/ACP dispersed in the cytoplasm through the overexpressed CD44 receptor that is actively targeted into human lung cancer cells (A549 cells). Meanwhile, the viability of A549 cells was significantly inhibited in vitro . The prepared HA-FCNs and HA-FCNs/ACP both exhibit excellent targeted bioimaging performance on cancer cells. Hence, the as-prepared nanoparticles have promising applications in treating tumor disease.
研究领域:
纳米技术
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癌症治疗
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生物医学工程
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材料科学
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药学
✓ 已验证
产品关联
DOI
高影响因子
ARCHIV DER PHARMAZIE
·
2022
·Vol. 355
·期 7
·2100465
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IF 4.613
Yating Guo,Xiaoding Jiang,Qi Chang,Zhihong Xiao,Zhuo Chen,Dejian Jiang,Gaoyun Hu,Qianbin Li
A series of novel pyrazolo[3,4- b ]pyridine derivatives were designed, synthesized, and biologically evaluated for anti-lung cancer activity. Structure–activity relationship and AutoGPA models were constructed based on the in vitro antiproliferative potency of the compounds against a human lung adenocarcinoma cell line (A549). Compound 9d exhibits improved potency for A549 cell growth inhibition (3.06 ± 0.05 μM) compared with A-769662 (45.29 ± 2.14 μM). Compound 9d can elevate the phosphorylation levels of adenosine monophosphate-activated protein kinase (AMPK) and its substrate acetyl-CoA carboxylase and reduce the level of phosphorylated ribosomal S6 kinase (p-70S6K) at 1 μM, which is comparable to the activity of A-769662 at 20 μM. 9d induced G2/M cell cycle arrest, which was rescued when co-incubated with “Compound C,” a potent AMPK inhibitor. Taken together, compound 9d showed potential anti-lung cancer activity via inducing cell cycle arrest by regulation of the AMPK/70S6K pathway in A549 cells, which could provide a new lead for the discovery of anti-lung cancer agents.
研究领域:
药物化学
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癌症研究
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药理学
✓ 已验证
DOI
PubMed
高影响因子
RUSSIAN JOURNAL OF GENERAL CHEMISTRY
·
2022
·Vol. 92
·期 10
·2119-2131
·
IF 0.779
Wang Yanyan,Chen Ruicheng,Hu Yiping,Jiao Shulin,Zou Zhihong
Abstract In this study, a novel series of 7-azaindole-1,2,3-triazole bearing N -benzamide derivatives 3a – 3r were synthesized and fully characterized by 1 H NMR, 13 C NMR, and MS. The prepared compounds were tested against A549 and HepG2 cell lines by using MTT assay in vitro anticancer activity. Compounds 3d , 3l , 3q , and 3r exhibited the most promising, with IC 50 (7.83, 7.58, 9.47, and 8.65 μM, respectively) against A549 compared with Gefitinib (IC 50 , 6.77 μM) and IC 50 (6.98, 6.69, 10.18, and 7.97 μM, respectively) against HepG2 compared with Sorafenib (IC 50 , 5.65 μM). Further molecular docking studies showed that compounds 3d , 3l , 3q , and 3r can bind well to protein targets 3LXY, 4AGD, and 3WZE, so these compounds have the potential to be developed into multi-targeted kinase inhibitor.
研究领域:
药理学
·
化学
·
肿瘤学
✓ 已验证
DOI
高影响因子
MICROCHEMICAL JOURNAL
·
2025
·
IF 5.1
Xue-Bo Hu,Yi-Peng Zhang,Zi-He Jin,Yi-Xiao Zhang,Yu-Ling Wang,Xiao-Long Fu,Jun-Tao Cao,Yan-Ming Liu
Three-dimensional cell culture has been considered as a powerful tool to achieve the in-vitro investigation that can mimics the cell behaviors and functions in body. With the advancement on this field, the requirements on applying effective identification and quantification strategy for real-time monitoring of cells are becoming more urgently. Therefore, we developed a PEDOT@Pt-based antifouling electrochemical sensor and collagen hydrogel integrated 3D platform. Among the 3D platform, the PEDOT@Pt-based electrochemical sensor presented high performance toward reactive oxygen species (hydrogen peroxide), with a high sensitivity of 176.0 nA/μM in the linear range of 100 nM to 100 μM, and a low detection limit of 43.1 nM. Besides, under the simulated cell culture environment, the electrochemical performance retained up to 70.8 % of the original performance, demonstrating good antifouling property. As a proof of concept, the A549 and HeLa cells were cultured into the 3D platform and the real-time monitoring of cell-released reactive oxygen species were further conducted. More importantly, the reactive oxygen species release behavior of cells under different stimulation were also explored within the 3D integrated platform, which is expected to enable precise biochemical analysis of cells under the in vivo -like microenvironment.
研究领域:
生物传感器
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电化学
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细胞生物学
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生物工程
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分析化学
✓ 已验证
产品关联
DOI
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2021
·
IF 6.53
Jinzhi Xu,Yan Xu,Lixin Sun,Bei Lu,Xi Yan,Zhonghao Wang,Tong Zhang
Introduction The development of multidrug resistance (MDR) is a major cause for the failure of chemotherapy, which requires the aid of nanomedicine. Methods Here in our study, a Cu 2+ based metal-organic framework (COF) was firstly developed and employed as a carrier for the delivery of glucose oxidase (GOx) and doxorubicin (Dox) (COF/GOx/Dox) for the therapy of MDR lung cancers. Results Our results showed that the GOx can catalyze glucose and produce H 2 O 2 . In the mean time, the Cu 2+ can react with GSH and then transform into Cu + , which resulted in GSH depletion. Afterwards, the produced Cu + and H 2 O 2 trigger Fenton reaction to generate ROS to damage the redox equilibrium of cancer cells. Both effects contributed to the reverse of MDR in A549/Dox cells and finally resulted in significantly enhanced in vitro/in vivo anticancer performance. Discussion The combination of glutathione depletion/reactive oxygen species elevation might be a promising strategy to enhance the efficacy of chemotherapy and reverse MDR in cancers.
研究领域:
纳米医学
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癌症治疗
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药学科学
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生物化学
✓ 已验证
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2019
·
IF 3.775
Jie Zhang,Yifan Song,Yuan Liang,Haoyang Zou,Peng Zuo,Mi Yan,Siyuan Jing,Tiezhu Li,Yongjun Wang,Da Li,Tiehua Zhang,Zhengyi Wei
Cucurbitacin IIa (CuIIa), a tetracyclic triterpenoid harboring anticancer activity, was investigated in A549 cells to reveal its mechanism of targeting on epidermal growth factor receptor (EGFR) signaling pathway. Results showed that CuIIa was capable of inducing apoptosis and cell cycle arrest at G2/M phase. The transcription of EGFR pathway genes and their proteins accumulation was inconsistently influenced by CuIIa. Notably, transcription of Raf1 was significantly upregulated, nevertheless, MEK1 and ERK1 were significantly downregulated. On the other hand, the accumulation of the total and phosphorylated proteins of the most members in EGFR-mitogen-activated protein kinase (MAPK) pathway, as well as CylclinB1 and survivin were also shifted by CuIIa treatment. Remarkably, total MEK remained constant but survivin completely degraded. Moreover, phosphorylated BRAF continuously increased while Raf1 and MEK decreased continuously. CuIIa was further confirmed to be a tyrosine kinase inhibitor (TKI) of EGFR by kinase inhibition assay. The results of molecular simulation showed that the long side chain of CuIIa occupied the binding pocket of EGFR and the ligand was stabilized at the active site of EGFR. In view of the results above, it is suggested that CuIIa inhibits cell proliferation by interfering the EGFR-MAPK signaling pathway.
研究领域:
肿瘤学
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细胞生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL BIOLOGY
·
2022
·
IF 3.889
Feng-guo Zhai,Qi-chao Liang,Yi-yan Wu,Jia-qi Liu,Jia-wei Liu
Context Red ginseng polysaccharide (RGP) is an active component of the widely used medicinal plant Panax ginseng C. A. Meyer (Araliaceae), which has displayed promising activities against cancer cells. However, the detailed molecular mechanism of RGP in ferroptosis is still unknown.Objective This study evaluates the effects of RGP in cancer cells.Materials and methods A549 and MDA-MB-231 cells were used. Cell proliferation was measured by CCK-8 assay after being treated with RGP at concentrations of 0, 50, 100, 200, 400, 800 and 1600 μg/mL at 0, 12, 24 and 48 h. Lipid reactive oxygen species (ROS) levels were assessed by C11-BODIPY assay. The control group was treated with PBS.Results RGP inhibited human A549 (IC50: 376.2 μg/mL) or MDA-MB-231(IC50: 311.3 μg/mL) proliferation and induced lactate dehydrogenase (LDH) release, promoted ferroptosis and suppressed the expression of GPX4. Moreover, the effects of RGP were enhanced by the ferroptosis inducer erastin, while abolished by ferroptosis inhibitor ferrostatin-1.Discussion and conclusions Our study is the first to demonstrate (1) the anticancer activity of RGP in human lung cancer and breast cancer. (2) RGP presented the anti-ferroptosis effects in lung and breast cancer cells via targeting GPX4.
研究领域:
肿瘤学
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药理学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2022
·Vol. 11
·期 3
·667-674
·
IF 7.571
Zheng Zhang,Weichen Yan,Yuanhui Ji
Cisplatin (CDDP) is one of the most frequently used chemotherapeutic drugs due to its broad-spectrum and potent antitumor activity. Unfortunately, inactivation due to glutathione (GSH) substances and insufficient cellular uptake of CDDP greatly hinder its clinical applications. Herein, manganese dioxide (MnO2) was reported as an efficient glutathione (GSH) consumption material for promoting the accumulation and preventing premature leakage of CDDP in tumor cells. In this work, γ-polyglutamic acid/cisplatin (PGA/CDDP) conjugates and PGA/CDDP nanoparticles (NPs) were respectively constructed via the ligand exchange reaction and electrostatic interaction. Furthermore, PGA/CDDP NPs were in situ coated with MnO2 (PGA/CDDP@MnO2 NPs) through the redox reaction of the residual carboxyl group (–COOH) and potassium permanganate (KMnO4). As a result, the PGA/CDDP@MnO2 NPs achieved a satisfactory drug-loading efficiency (ca. 37.26%) and multi-responsive controlled drug release. Remarkably, the MnO2 shells exhibited excellent performance for efficient glutathione (GSH) consumption and significantly enhanced the killing effect (ca. 2–3 times) in human lung cancer cells (A549) compared with pure CDDP. Moreover, it was observed that PGA/CDDP@MnO2 NPs could also inhibit the migration and invasion of A549 cells. Overall, these remarkable performances of PGA/CDDP@MnO2 NPs make MnO2 promising for controlled drug release and intelligent anticancer therapy.
研究领域:
药学
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材料科学
·
癌症研究
·
纳米技术
✓ 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）