INORGANICA CHIMICA ACTA
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2025
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IF 3.2
Peishan Huang,Wenhui Deng,Qiong Wu,Wanwan Hong,Jing Liu,Jiangbo Liang,Bin Zhao,Wenjie Mei
Herein, four ruthenium(II) complexes, [Ru(L) 2 (PEIP)(CH 2 ) 4 Br)](ClO 4 ) 2 (L = phen, 1 ; bpy, 2 , PEIP = 2-(2-phenyl-ethenyl)-1 H -imidazole-[4,5 f ][1,10]phenanthroline) and [Ru(L) 2 (PEIP)(CH 2 ) 4 Erianin)](ClO 4 ) 2 (L = phen, 1E ; bpy, 2E ) have been synthesized and investigated as promising inducer to promote conformation inversion of AS1411 G4 DNA. All of these complexes can bind and stabilize AS1411 G4 DNA. Subsequent investigations reveal that in the presence of 1 and 1E, the described circular dichroism signal of AS1411 G4 DNA was reversed. Furthermore, it is discovered that in the presence of 1 and 1E, AS1411 G4 DNA can condense to a somewhat loose nano-network. Moreover, the analysis using molecular docking demonstrates that the conformation inversion of AS1411 G4 DNA is largely dependent on the binding sites of 1 and 1E. In conclusion, these complexes will be used for tumor diagnostics in the clinical context because of their capacity to stably bind AS1411 G4 DNA and dramatically boost its fluorescence emission. Besides, these complexes show promise as inducers of AS1411 G4 DNA conformational inversion.
研究领域:
生物化学
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药物化学
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核酸化学
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产品关联
DOI
高影响因子
DALTON TRANSACTIONS
·
2014
·Vol. 43
·期 24
·9216-9225
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IF 4.097
Qiong Wu,Tianfeng Chen,Zhao Zhang,Siyan Liao,Xiaohui Wu,Jian Wu,Wenjie Mei,Yanhua Chen,Weili Wu,Lingli Zeng,Wenjie Zheng
Two arene Ru(II) complexes coordinated by 2-(3-methoxyphenyl)imidazole[4,5-f][1,10]phenanthroline, [(η6-RC6H5)Ru(m-MOPIP)Cl]Cl (R = H, 1; R = CH3, 2), have been prepared under microwave irradiation; the crystal structure of 2 exhibits a typical “piano stool” conformation, with bond angles for N1–Ru1–Cl1 86.02 (14)° and N2–Ru1–Cl1 84.51 (14)°. The Ru–C distance for the Ru atom bound to the benzene ring is about 0.2178(8) nm, and the average Ru–N distance for Ru atom to the two chelating N atoms is about 0.2092(4) nm. The evaluation of in vitro anticancer activities revealed that these synthetic Ru(II) complexes selectively inhibited the growth of HepG2 hepatocellular carcinoma cells, with low cytotoxicity toward LO2 human normal liver cells. The results demonstrated that the complexes exhibited great selectivity between human cancer and normal cells by comparing with the ligand m-MOPIP. Furthermore, complexes 1 and 2 could bind to c-myc G4 DNA in groove binding mode in promising affinity, and the insertion of the methyl groups in the arene ligand contributed to strengthen the binding affinity. This was also confirmed by molecular docking calculation and 1H NMR analysis which showed that both 1 and 2 can bind in the loop constructed by A6–G9 and G21–A25 base pairs in c-myc G4 DNA to block the replication of c-myc oligomer. Taken together, these results suggest that arene Ru(II) complexes display application potential as small molecule inhibitors of c-myc G4 DNA.
研究领域:
无机化学
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药物化学
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癌症研究
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DNA相互作用
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2016
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IF 3.169
Haihui Shen,Bo Zhang,Huiyan Xu,Yue Sun,Qiwang Wu,Hong Shen,Yingchun Liu
Some natural heterocyclic alkaloids containing planar group show potential to complex with specific promoter region of protooncogene for stabilizing the G-quadruplex (G4) structure which nowadays promises to be a target in anticancer drug design. However, in view of the polymorphic characteristics and structural complexity of heterocyclic alkaloids, it is desirable to develop high-throughput and low-consumption approach for anticancer drug screening. In this paper, an intensive study on alkaloid ligand/G4 DNA interaction has been conducted, demonstrating that the end-stacking interaction is the favorable binding mode between the oncogene-related Pu22 G4 DNA and the heterocyclic alkaloid ligand. Based on structural feasibility and energy minimization, a ligand displacement assay for screening alkaloid ligand in stabilizing the oncogene target G4 has been developed, which also helps to facilitate the assessment of drug specificity. Coupled with microfluidic-based DNAzyme-catalytic chemiluminescence detection, the approach showed the advantages of high sensitivity, high throughput with low sample and reagent consumptions.
研究领域:
药理学
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分子生物学
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药物发现
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癌症研究
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DOI
PubMed
高影响因子
ANALYST
·
2024
·
IF 3.6
Chengchen Tan,Xiaolong Yan,Xingchang Lu,Jianxiu Wang,Xinyao Yi
Breast cancer, as a malignant tumor with the highest incidence in the world, poses a great threat to human life and health. Early diagnosis of breast cancer may help enhancing the survival rate. In this work, a colorimetric and fluorescent dual-mode biosensor based on CRISPR-Cas12a system was constructed for the detection of breast cancer biomarker BRCA1. The intact G4 DNA could form DNAzyme in the assistance of K+ and hemin, catalyzed the oxidation of o-phenylenediamine (OPD) under the assistance of hydrogen peroxide (H2O2), and generate the oxidation product 2,3-diaminophenazine (DAP) with obvious absorption and fluorescence peaks. The presence of the target BRCA1 can activate the trans-cleavage activity of CRISPR-Cas12a, cleaving the G4 DNA and inhibiting the catalytic oxidation of OPD. The target BRCA1 was quantitatively determined by detecting both the absorbance and fluorescence intensity of DAP. Compared with single signal analysis, dual-signal output mode provided more reliable detection results. The detection limits were calculated to be 0.615 nM for colorimetric method and 0.289 nM for fluorescence method. The dual-mode biosensor showed good selectivity for BRCA1 and can resist the interference of complex substrates, which has great potential in biomedical detection.
研究领域:
生物医学工程
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分子生物学
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癌症研究
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生物技术
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Meng-Ting She,Jia-Wei Yang,Bo-Xin Zheng,Wei Long,Xuan-He Huang,Jun-Ren Luo,Ze-Xin Chen,Ao-Lu Liu,Dong-Peng Cai,Wing-Leung Wong,Yu-Jing Lu
A series of new mitochondrial-selective fluorescent probe was designed and synthesized based on the integration of two planar molecular scaffolds of benzo-indole/indole with a p -substituted styrene moiety. The small-sized probes are flexible and rotatable via an ethylene bridge. The restriction of free rotation upon interaction with targeting biomolecules of G-quadruplexes in mitochondria generates strong emission in visible range (575–615 nm). Cell imaging study showed that the ligands are targeting mitochondria but not nucleus. Competition experiments showed that the ligand BYM is highly selective towards mitochondrial G4-DNA structures against other non-G4 nucleic acid structures including single-/double-stranded DNA and hairpin. The equilibrium binding constant ( K eq ) of BYM interacting with mitochondrial G4-DNA (mt6363, K eq = 10.8 × 10 6 M −1 ) is almost 1000-fold higher than that of mitochondrial double-stranded DNA ( K eq = 0.01 × 10 6 M −1 ). The probe also showed high sensitivity (LOD = 1.52 nM) and good linear relationship (R 2 = 0.9983) with the mitochondrial G4-DNA. The delivery of BYM to mitochondria is not mitochondrial membrane potential dependent but mainly through the permeability transition pore on the mitochondrial inner membrane. In addition, BYM exhibits low cytotoxicity against a number of human cancer and noncancerous cells, indicating that BYM could be a good ligand for bioorthogonal study in live cells by targeting the mitochondrial G4-DNA structures. In the present study, BYM was demonstrated in monitoring the dynamic process of mitochondrial autophagy. The small-sized fluorescent probe possessing high photostability, selectivity and sensitivity targeting mitochondrial G-quadruplexes may able to provide a useful chemical tool for real-time study of mitochondrial functions in live cells.
研究领域:
细胞生物学
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分子生物学
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生物医学工程
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分析化学
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产品关联
DOI
高影响因子
ACS Sensors
·
2019
·
IF 6.944
Lin Shi,Yudie Sun,Lan Mi,Tao Li
Portable chemiluminescence (CL) imaging with a smartphone has shown a great promise for point-of-care testing of diseases, especially for acute myocardial infarction (AMI), which may occur abruptly. A challenge remains how to improve the imaging sensitivity that usually is several orders of magnitude lower than those of counterpart methodologies using the sophisticated equipment. Toward this goal, here, we report the target-triggered in situ growth of AuNP@hairpin-DNA nanoprobes into spherical nucleic acid enzymes (SNAzymes), which serve as both nanolabels and amplifiers for portable CL imaging of microRNAs (miRNAs) with an ultrahigh sensitivity comparable to that of the instrumental measurement under same conditions. A G-quadruplex (G4) DNA dense layer is dynamically produced on the gold nanocore via a DNAzyme machine-driven hairpin cleaving and captures the cofactor hemin to form the SNAzymes with higher peroxidase activity and stronger nuclease resistance than the commonly used G4 DNAzymes. The matured SNAzymes are then utilized as catalytic labels in a luminol-artesunate CL system for miRNA imaging with a smartphone as the portable detector. In this way, two AMI-related miRNAs, miRNA-499 and miRNA-133a, are successfully detected in real patients’ serum with a naked eye-visualized CL change at 10 fM, showing a 5 order of magnitude improvement on the sensitivity of visualizing the same disease markers in clinical circulating blood as compared to the reported strategy. In addition, a good selectivity of our developed CL imaging platform is demonstrated. These unique features make it promising to employ this portable imaging platform for clinical AMI diagnosis.
研究领域:
生物技术
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生物化学
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纳米技术
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即时诊断
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医疗器械
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分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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