TALANTA
·
2023
·
IF 6.1
Qinsheng Chen,Qinwei Lu,Lianglong Zhang,Chenhan Zhang,Jingxian Zhang,Yu Gu,Qingxia Huang,Huiru Tang
Consistent retention time ( t R ) of metabolites is vital for identification in metabolomic analysis with ultrahigh-performance liquid-chromatography (UPLC). To minimize inter-experimental t R variations from the reversed-phase UPLC-MS, we developed an endo genous r etention- i ndex (endoRI) using in-sample straight-chain acylcarnitines with different chain-length ( L C , C0–C26) without additives. The endoRI-corrections reduced the t R variations caused by the combined changes of mobile phases , gradients, flow-rates, elution time, columns and temperature from up to 5.1 min–0.2 min for most metabolites in a model metabolome consisting of 91 metabolites and multiple biological matrices including human serum, plasma, fecal, urine, A549 cells and rabbit liver extracts. The endoRI-corrections also reduced the inter-batch and inter-platform t R variations from 1.5 min to 0.15 min for 95 % of detected features in the above biological samples. We further established a quantitative model between t R and L C for predicting t R values of acylcarnitines when absent in samples. This makes it possible to compare metabolites’ t R from different t R databases and the UPLC-based metabolomic data from different batches.
研究领域:
分析化学
·
代谢组学
·
生物化学
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DOI
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2021
·Vol. 46
·期 3
·1295-1307
·
IF 3.591
Zhi-Gang Yin,Xiong-Wei Liu,Hui-Juan Wang,Min Zhang,Xiong-Li Liu,Ying Zhou
A highly efficient synthesis of structurally diverse ortho-acylphenol–diindolylmethane hybrids 3 using carboxylic acid-activated chromones as versatile synthetic building blocks is reported here for the first time, through 1,4-nucleophilic addition and followed by a decarboxylation and pyrone ring opening reaction process. The newly synthesized compounds were evaluated for their in vitro anticancer activity, and most of the compounds displayed good anticancer activities against four tested tumor cells (A549, PC-3, NCI-H1299, Caco-2). Among these compounds, compound 3t displayed the most potent and broad-spectrum anti-proliferative inhibition against the tested cell lines, especially A549 cells, and was more potent than arundine and cisplatin drugs, and had selectivity in cancer cells compared to MRC-5 and HK-2 normal cells. Preliminary mechanism studies showed that compound 3t exerted an anti-tumor effect in A549 cells by inhibiting the proliferation, colony formation and migration of A549 cells, and inducing cycle arrest at the G0/G1 phase and apoptosis. Furthermore, treatment of A549 cells with compound 3t caused increased ROS content and induced MMP collapse; western blot analysis showed that the expression level of p53 was significantly increased; Bax/Bcl-2 ratio and Cyt c were increased, and caspase-9, -3, and PARP were cleaved. These studies showed that compound 3t could induce apoptosis of A549 cells through the mitochondrial pathway, which was related to the activation of p53 and the generation of ROS. Thus, our results indicate that compound 3t may be used as a promising skeleton for the development of new anti-tumour drugs.
研究领域:
药物化学
·
肿瘤学
·
药学
·
细胞生物学
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DOI
高影响因子
Nanoscale
·
2015
·Vol. 8
·期 1
·104-116
·
IF 7.394
Wenxiu Hou,Xin Zhao,Xiaoqing Qian,Fei Pan,Chunlei Zhang,Yuming Yang,Jesús Martínez de la Fuente,Daxiang Cui
The development of visual tumor theranostic nanoparticles has become a great challenge. In this study, D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was conjugated to acid-sensitive cis-aconitic anhydride-modified doxorubicin (CAD) to obtain pH-sensitive anti-tumor prodrug nanoparticles (TCAD NPs) via self-assembling. Subsequently, the photosensitizer chlorin e6 (Ce6) was loaded into the resulting prodrug nanoparticles to prepare a novel tumor near-infrared fluorescence imaging and chemo–photodynamic combination therapy system (TCAD@Ce6 NPs). An accelerated release of doxorubicin (DOX) and chlorin e6 (Ce6) from the TCAD@Ce6 NPs could be achieved due to the hydrolysis of the acid-sensitive amide linker under mild acidic conditions (pH = 5.5). An in vitro experiment showed that A549 lung cancer cells exhibited a significantly higher uptake of DOX and Ce6 by using our delivery system than the free form of DOX and Ce6. An in vivo experiment showed that TCAD@Ce6 NPs displayed better tumor targeting gathering through the enhanced permeability and retention (EPR) effect than free Ce6, thus improving fluorescence imaging. Moreover, the chemo–photodynamic combination therapy of TCAD@Ce6 NPs combined with near-infrared laser irradiation was confirmed to be capable of inducing high apoptosis and necrosis of tumor cells (A549) in vitro and to display a significantly higher tumor growth suppression in the A549 lung cancer-bearing mice model. Furthermore, compared with exclusive chemotreatment (DOX) or photodynamic treatment (Ce6), our system showed enhanced therapeutic effects both in vitro and in vivo. In conclusion, the high performance TCAD@Ce6 NPs can be used as a promising NIR fluorescence imaging and highly effective chemo–photodynamic system for theranostics of lung cancer, etc. in the near future.
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2024
·
IF 4.5
Ping Sun,Na Xu,Xue Zhang,Yun-Fei Gao,Jia-Yin Zhang,Qi-Ming Zhang,Chen Liang,Ri-Lei Yu,Ya-Mu Xia,Wei-Wei Gao
In this work, we rationally designed and synthesized two novel triazene-amonafide derivatives 2-(2-(diisopropylamino)ethyl)-5-(3,3-dimethyltriaz-1-en-1-yl)-1H-benzo[ de ]isoquinoline-1,3(2H)-dione ( D-11 ) and 5-(3,3-diethyltriaz-1-en-1-yl)-2-(2-(diisopropylamino)ethyl)-1H-benzo[ de ]isoquinoline-1,3(2H)-dione ( D-12 ) as potential antitumor agents. The DNA damage induced by the intercalation mode of D-11 ( D-12 ) towards DNA was electrochemically detected through the construction of efficient biosensors. The consecutive processes of reversible redox of naphthylimide ring and irreversible oxidation of triazene moiety were elucidated on the surface of glassy carbon electrode (GCE) by CV, SWV, and DPV methods. Electrochemical biosensors were obtained through the immobilization of ct DNA, G-quadruplexes, poly(dG), and poly(dA), respectively, on the clean surface of GCE. After the incubation of biosensors with D-11 or D-12 , the peaks of dGuo and dAdo decreased prominently, and the peak of 8-oxoGua appeared at +0.50 V, suggesting that the interaction between D-11 ( D-12 ) and DNA could result in the oxidative damage of guanine. Unexpected, the as-prepared DNA biosensor possessed satisfactory anti-interference property and good practicability in real samples. UV–vis and fluorescence spectra, and gel electrophoresis assays were employed to further confirm the intercalation mode of D-11 ( D-12 ) towards DNA base pairs. Moreover, D-11 was proved to exhibit stronger anti-proliferation activity than mitionafide and amonafide against both A549 and HeLa cell lines.
研究领域:
药物化学
·
生物化学
·
分子生物学
·
癌症研究
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2012
·
IF 7.404
Yanfang Zhou,Bin Yang,Xianyue Ren,Zhenzhen Liu,Zheng Deng,Luming Chen,Yubin Deng,Li-Ming Zhang,Liqun Yang
A series of hyperbranched cationic amylopectin derivatives conjugated with 1,2-ethylenediamine, diethylenetriamine and 3-(dimethylamino)-1-propylamine residues, named as EDA-Amp, DETA-Amp and DMAPA-Amp, were synthesized by the N,N’- carbonyldiimidazole activation method at room temperature. Their structures were characterized by FTIR and 1 H NMR analyses, and their buffering capability was assessed by acid-base titration. The amylopectin derivatives exhibited better blood compatibility and lower cytotoxicity when compared to branched polyethyleneimine (bPEI) in the hemolysis and MTT assays . Atomic force microscopy and optical microscopy confirmed that the amylopectin derivatives exhibited lower damage for erythrocytes than bPEI. The amylopectin derivatives could bind and condense plasmid DNA (pDNA) to form the complexes with the size ranging from 100 to 300 nm. The resultant complexes showed higher transfection efficiency in 293T cells than in A549 cells. The DMAPA-Amp derivative-mediated gene transfection for Forkhead box O1 exhibited higher protein expression than that of the EDA-Amp and DETA-Amp derivatives in 293T cells, which was analyzed by western blot , flow cytometry and Hoechst staining assay. On the basis of these data, amylopectin derivatives exhibit potential as nonviral gene vectors .
研究领域:
药学
·
分子生物学
·
生物技术
·
基因治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2021
·
IF 7.46
Kai-Xin Song,Dong Chen,Zi-Yang Liao,Xuan Yu,Fei-Fei Guo,Ri-Lei Yu,Meng-Zhen Xu,Ya-Mu Xia,Wei-Wei Gao
In this work, an efficient electrochemical biosensor for the detection of DNA damage induced by the interaction of a novel antitumor agent AD-NU was investigated by CV , DPV and SWV methods. The GCE was modified with calf thymus DNA, G-quadruplexes, poly dA and poly dG, respectively. Among all the candidates, compound AD-NU was the optimum ligand because of the minimum energy when binding to DNA or TOP II by molecular docking. The electrochemical analysis revealed the redox mechanism of AD-NU on the GCE surface, which included two consecutive reversible processes of 9,10-diquinone and irreversible redox of nitroso group . The DNA damage caused by AD-NU was investigated by comparing the intensity changes of dGuo and dAdo oxidation peaks in DNA strands, and monitoring the appearance of peak for oxidative product 8-oxoGua. Further confirmation for the interaction between AD-NU and DNA was performed by UV–vis absorption and fluorescence titration, which implied the intercalation of AD-NU into DNA base pairs with a high affinity constant ( K b = 13.7 ×10 5 M −1 ). The electrophoresis also revealed the potency of AD-NU to cleave and unwind DNA strands. Finally, AD-NU was proved to have good antiproliferative activity toward tumor cells, with IC 50 values of 3.0 μmol ∙ L −1 for A549 cell lines and 3.3 μmol ∙ L −1 for Hela cell lines, superior to MTZ reference.
研究领域:
电化学
·
生物传感器
·
分子生物学
·
癌症研究
·
分析化学
·
药理学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）