MEDICINAL CHEMISTRY RESEARCH
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2019
·Vol. 28
·期 6
·892-899
·
IF 1.72
Sun Li,Chu Xiang-Wu,Liu Chun-mei,Sheng Li-Xin,Chen Zhuan-Xin,Cheng Ke-Guang
As pharmacophore hybridization has been used frequently in the discovery of new drugs, ursolic acid/glycyrrhetinic acid-uracil/thymine hybrids have been synthesized and evaluated their antiproliferative activity by the MTT assay. The results displayed that, the hybrids of glycyrrhetinic acid ( 7a – 7b to 10a – 10b ) exhibited slightly better antiproliferative activity than that of ursolic acid hybrids ( 3a – 3b to 6a – 6b ). Two single glycyrrhetinic acid-thymine hybrids ( 8a and 10a ) possessed good antiproliferative activity against tested A549 cell line (IC 50 = 10.7 and 18.3 µM, respectively). And three hybrids ( 3a , 5a , and 10b ) exhibited about 80% inhibitory ratio against tested Hela cell line.
研究领域:
药物化学
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肿瘤学
·
分子生物学
·
药理学
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DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Tao Ai,Mingling Yu,Yicheng Dai,Ruipu Yao,Ling N. Jin,Yuanyuan Yu,Xinbin Qiu,Peixin Huang,Xifen Zhu,Jianteng Sun,Lizhong Zhu
This study investigates the uptake, biotransformation, and phytotoxicity of sulfadiazine (SDZ) and its acetyl derivative N4-acetylsulfadiazine (NASDZ) in rice. Results showed that rice was more tolerant to NASDZ, with lower malondialdehyde and reactive oxygen species levels but higher antioxidant enzyme activities (SOD, POD, and CAT). The maximum accumulations of SDZ in roots and shoots were 19.3 ± 1.0 and 3.6 ± 1.1 μg/g, while NASDZ were 18.6 ± 2.5 and 3.5 ± 1.4 μg/g, respectively. SDZ exposure generated more metabolic intermediates, including deamination, hydroxylation, glycosylation, acetylation, and formylation products, while NASDZ metabolism was documented for the first time. Key genes involved in biotransformation include cytochrome P450, acetyltransferase, glycosyltransferases, and methyltransferase. Density functional theory calculations showed structural differences affecting reactive sites and intermediates. SDZ disrupted lipid metabolism, while NASDZ altered carbohydrate and amino acid pathways, highlighting their selective effects on rice metabolism. Our data help understand sulfonamide biotransformation and phytotoxicity in rice.
研究领域:
环境科学
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植物生理学
·
毒理学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Xubao Jiang,Suisui Wang,Xiang Zheng Kong
Pyrimidines, in particular uracil (UL) and 5-fluorouracil (5FU), are well known anticancerogens and widely used against a variety of cancers. An important concerning issue has been their monitoring and detection in order to adequately control their doses and to minimize their health hazards. Among a variety of methods developed, fluorescence sensing is gaining more attention because of its accuracy, easy operation, and straight visuability. However, in most of the reported studies, the sensors are made from transition metals with sophisticated multi-processes; polymers, particularly biopolymers, are hardly available. We demonstrate herein that aqueous solution of poly(ethylene glycol) (PEG), a commonly known biopolymer, is highly emissive under excitation of 280 nm. While the solutions of selected pyrimidines, i.e. UL and 5FU, are non-emissive under the same excitation, their addition to PEG solution, however, brings about a distinct and concentration dependent quenching for PEG emission. PEG was then used as sensor with good stability for UL and 5FU detections in water. The tests were also done by spiking 5FU in tap water, milk and synthetic urine, confirming that 5FU was practically fully recovered in all the cases. The quenching was ascribed to the interaction between PEG clusters and the heteroatoms on pyrimidine molecules through hydrogen bonding, which is supported by multi-technical analyses, including NMR, FTIR and cluster size tests by DLS. This work provides therefore a full green, easy to operate, low-costing, novel and reliable protocol for pyrimidine monitoring and detection, with the quenching mechanism interpreted based on multi-technical characterizations.
研究领域:
生物化学
·
医学检测
·
材料科学
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产品关联
DOI
高影响因子
TALANTA
·
2017
·
IF 4.162
Yu Hou,Xue Liu,Xiuping Tang,Tianze Li,Qiuhua Wu,Yuchun Jiang,Jie Yi,Guolin Zhang
A facile and sensitive fluorescence protocol for nucleobase detection was developed based on carbon nanodot (CD) chemosensors . The novel fluorescent CDs were prepared using four kinds of nucleobases (including adenine , guanine , thymine and cytosine) as separate carbon sources via simple hydrothermal strategy. The quantum yield of adenine CDs (A-CDs), guanine CDs (G-CDs), thymine CDs (T-CDs) and cytosine CDs (C-CDs) was checked as 15.1%, 28.3%, 10.6% and 11.7%, respectively. Four CDs can recognize their complementary nucleobases based on the principle of complementary base pairing. Their fluorescence was linearly quenched with the increase of nucleobase concentrations under optimal conditions. Combining the calibration curve , quantitative assay of nucleobase in solution can be realized. For example, A-CDs could determine thymine in the concentration range of 2–20 mM with a detection limit of ca. 0.053 mM, and the linear equation is fitting as (I 0 −I) / I = 0.01961 × C T (mM) + 0.01756 (R 2 = 0.994). Thymine can induce the fluorescence lifetime of A-CDs decreasing from 5.58 to 3.34 ns, indicating a dynamic quenching mechanism. The novel nucleobase sensors were also evaluated in specific solution environment. A-CDs showed a relatively minor relative standard deviation (< 4.0%) in fetal calf serum solution, indicating a high accuracy and credibility of the sensing system. In view of the excellent sensitivity, preferable biocompatibility as well as simple constructing method, the sensing platform derived from the nucleobase-based CDs present great potential in biological sensing applications.
研究领域:
生物化学
·
分析化学
·
纳米技术
✓ 已验证
DOI
高影响因子
Nature Communications
·
2019
·Vol. 10
·期 1
·1-14
·
IF 11.878
Ou Juanjuan,Peng Yuan,Yang Weiwen,Zhang Yue,Hao Jie,Li Fu,Chen Yanrong,Zhao Yang,Xie Xiong,Wu Shuang,Zha Lin,Luo Xi,Xie Ganfeng,Wang Liting,Sun Wei,Zhou Qi,Li Jianjun,Liang Houjie
The efficacy of Fluorouracil (FU) in the treatment of colorectal cancer (CRC) is greatly limited by drug resistance. Autophagy has been implicated in chemoresistance, but the role of selective autophagic degradation in regulating chemoresistance remains unknown. In this study, we revealed a critical role of ABHD5 in charging CRC sensitivity to FU via regulating autophagic uracil yield. We demonstrated that ABHD5 localizes to lysosome and interacts with PDIA5 to prevent PDIA5 from interacting with RNASET2 and inactivating RNASET2. ABHD5 deficiency releases PDIA5 to directly interact with RNASET2 and leave RNASET2 in an inactivate state, which impairs RNASET2-mediated autophagic uracil yield and promotes CRC cells to uptake FU as an exogenous uracil, thus increasing their sensitivity to FU. Our findings for the first time reveal a novel role of ABHD5 in regulating lysosome function, highlighting the significance of ABHD5 as a compelling biomarker predicting the sensitivity of CRCs to FU-based chemotherapy.
研究领域:
肿瘤学
·
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
Metabolites
·
2022
·Vol. 12
·期 5
·410
·
IF 5.581
Jieping Zhang,Shaomin Zou,Yijing Zhang,Ziqing Yang,Wencong Wang,Manqi Meng,Junyan Feng,Peng Zhang,Lishi Xiao,Mong-Hong Lee,Lekun Fang
Chemoresistance limits treatment outcomes in colorectal cancer (CRC) patients. A dimeric metabolite of indole-3-carbinol, 3,3′-diindolylmethane (DIM) is abundant in cruciferous vegetables and has shown anticancer efficacy. The role of DIM in regulating chemosensitivity in CRC remains unknown. In this study, we demonstrated that DIM treatment inhibits the malignant progression of CRC. RNA sequencing indicated that pyrimidine synthesis genes are attenuated by DIM treatment. Stable 13C-labeled glucose tracing revealed that DIM inhibits de novo pyrimidine biosynthesis in CRC. DIM increases 5-FU cytotoxicity in CRC via regulation of the expression of pyrimidine metabolism-related genes. DIM synergizes with 5-FU to enhance its inhibitory effects on CRC both in vivo and in vitro. Our results suggest that DIM improves the therapeutic outcomes of FU-based chemotherapy in CRCs by inhibiting pyrimidine metabolism, identifying a new strategy for clinical therapy.Keywords:colorectal cancer;3,3′-Diindolylmethane;chemosensitivity;pyrimidine metabolism
研究领域:
肿瘤学
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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
JOURNAL OF CHEMICAL RESEARCH
·
2012
·
IF 0.633
Shuguang Zhou,Mingxia Xu,Siyu Ye,Dashuai Li,Jing Xu,Pei Mao,Jing Xiong
24 Aza-Michael adducts were synthesised in moderate to excellent yields by the addition of 5-substituted uracils to acrylates with ethylamine as a catalyst. Many of the adducts were obtained in almost quantitive yield without column chromatography. The procedure provideded an efficient approach to the synthesis of N-1 uracil adducts using acrylates as acceptors. The structures of the compounds were determined by 1H NMR, 13C NMR, mass spectra and X-ray crystallography analyses. The uracil unit is present in DNA and related natural products and has a broad spectrum of biological activity.
研究领域:
有机化学
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药物化学
·
生物化学
✓ 已验证
DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Yue-Ming Yu,Xue-Jie Li,Fan-Zhi Bu,Zhi-Long Zhao,Zhi-Yong Wu,Yan-Tuan Li
An integrated strategy by combining cocrystallization with nanotechnology is developed to optimize in vitro/vivo performances of marine antitumor drug cytarabine (ARA) and further obtain innovative insights into the exploitation of cocrystal alloy nanoformulation. Therein, the optimization of properties and synergistic effects of ARA mainly depends on assembling with uracil (U) and antitumor drug 5-fluorouracil (FU) into the same crystal by cocrystallization technology, while the long-term efficacy is primarily maintained by playing the superiority of nanotechnology. Along this line, the first cocrystal alloy of ARA, viz., ARA-FU-U (0.6:0.4), is successfully obtained and then transformed into a nanocrystal. Single-crystal X-ray diffraction analysis demonstrates that this cocrystal alloy consists of two isomorphic cocrystals of ARA, namely, ARA-FU and ARA-U, in 0.6:0.4 ratio. An R22(8) hydrogen-bonding cyclic system formed by a cytosine fragment of ARA with U or FU can protect and stabilize the amine group on ARA, laying the foundation for regulating its properties. The in vitro/in vivo properties of the cocrystal alloy and its nanocrystals are investigated by theoretical and experimental means. It reveals that both the alloy and nanocrystal can improve physicochemical properties and promote drug absorption, thus bringing to optimized pharmacokinetic behaviors. The nanocrystal produces superior effects than the alloy that helps to extend therapeutic time and action. Particularly, relative to the corresponding binary cocrystal, the synergistic antitumor activity of ARA and FU in the cocrystal alloy is heightened obviously. It may be that U contributes to reducing the degradation of FU, specifically increasing its concentration in tumors to enhance the synergistic effects of FU and ARA. These findings provide new thoughts for the application of cocrystal alloys in the marine drug field and break fresh ground for cocrystal alloy formulations to optimize drug properties.
研究领域:
药学
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生物医学工程
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2024
·
IF 10.7
Mei Zhao,Jingyi Guo,Zilin Chen,Fang Wang
5-formylcytosine (5 fC) and 5-carboxylcytosine (5caC) serve as key intermediates in DNA demethylation process with significant implications for gene regulation and disease progression . In this study, we introduce a novel electrochemical sensing platform specifically designed for the sensitive and selective detection of 5 fC and 5caC in DNA . Protein A-modified magnetic beads (ProtA-MBs) coupled with specific antibodies facilitate the immunorecognition and enrichment of these modified bases. Signal amplification is achieved through several chemical reactions involving the interaction between N 3 -kethonaxl and guanine , copper-free click chemistry for the attachment of dibenzocyclooctyne (DBCO)-Biotin, and the subsequent recognition by streptavidin-conjugated horseradish peroxidase (SA-HRP). The assay's readout is performed on a disposable laser-induced graphene (LIG) electrode, modified with the bead-antibody-DNA complex in a magnetic field , and analyzed using differential pulse voltammetry in a system employing hydroquinone (HQ) as the redox mediator and H 2 O 2 as the substrate. This immunosensor displayed excellent sensitivity, with detection limits of 14.8 fM for 5 fC across a 0.1–1000 pM linear range and 87.4 fM for 5caC across a 0.5–5000 pM linear range, and maintained high selectivity even in the presence of interferences from other DNA modifications . Successful application in quantifying 5 fC and 5caC in genomic DNA from cell extracts, with recovery rates between 97.7% to 102.9%, underscores its potential for clinical diagnostics. N 3 -kethoxal was used for the first time in an electrochemical sensor. This work not only broadens the toolkit for detecting DNA modifications but also provides a fresh impetus for the development of point-of-care testing (POCT) technologies.
研究领域:
分子生物学
·
分析化学
·
医学诊断
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Chemistry Frontiers
·
2024
·
IF 6
Jia Liu,Zhiyang Wang,Xiaowei Wu,Shanyue Wei,Yiming Xie,Jing Chen,Can-Zhong Lu
Owing to the unique properties of high porosity, outstanding chemical stability, and designable structures, vast applications of covalent organic frameworks (COFs) have been explored in a wide range of areas including energy storage, catalysis, gas separation, etc. Nevertheless, from the perspective of electrochemical sensing, the conductivity of COFs is not satisfactory. Here, a two-dimensional (2D) hybrid nanosheet combining a COF, a supramolecular host, and nanomaterials was constructed by assembling cucurbit[8]uril (CB8) onto the surface of the COF, and achieved in situ growth of uniformly dispersed AuNPs with the aid of the modulation effect of CB8 to synergistically enhance the sensing performance. By taking advantage of the abundant active loading sites and large specific area of the 2D-COF, excellent conductivity of AuNPs, and host–guest binding ability of CB8, the prepared COF/CB8/AuNPs is utilized to modify the glassy carbon electrode (GCE) as an advanced electrochemical sensor for simultaneous detection of structurally similar analytes, e.g. antineoplastic agent 5-fluorouracil (5-FU) and RNA base uracil (U) using differential pulse voltammetry, achieving detection limits down to the nanomolar level (e.g. 0.037 and 0.074 μM for 5-FU and U, respectively) and the physiologically relevant linear detection range within the sub-micromolar window. Impressively, the prepared COF/CB8/AuNPs/GCE sensor is considerably robust in complicated biofluids, allowing for detecting 5-FU and U in unprocessed native synthetic urine (SU) and whole fetal bovine serum (FBS), which remained highly challenging for electrochemical sensors. This study elucidates the integration of COFs with supramolecular host systems, paving the way for the development of advanced electrochemical sensors for rapid and onsite detection in pharmaceutical diagnostic applications.
研究领域:
材料科学
·
电化学
·
医学诊断
✓ 已验证
产品关联
DOI
高影响因子
Pharmaceuticals
·
2021
·Vol. 14
·期 11
·1194
·
IF 5.863
Min Li,Qingfeng He,Li Yao,Xiaofeng Wang,Zhijia Tang,Xiao Zhu,Hai-Shu Lin,Xiaoqiang Xiang
Propylthiouracil (PTU) is commonly prescribed for the management of hyperthyroidism and thyrotoxicosis. Although the exact mechanism of action is not fully understood, PTU is associated with hepatoxicity in pediatric population. Glucuronidation mediated by uridine 5′-diphospho-glucuronosyltransferases (UGTs), which possess age-dependent expression, has been proposed as an important metabolic pathway of PTU. To further examine the metabolism of PTU, a reliable HPLC-MS/MS method for the simultaneous quantification of PTU and its N-β-D glucuronide (PTU-GLU) was developed and validated. The chromatographic separation was achieved on a ZORBAX Extend-C18 column (2.1 × 50 mm, 1.8 μm) through gradient delivery of a mixture of formic acid, methanol and acetonitrile. The electrospray ionization (ESI) was operated in its negative ion mode while PTU and PTU-GLU were detected by multiple reaction monitoring (MRM). This analytical method displayed excellent linearity, sensitivity, accuracy, precision, recovery and stability while its matrix effect and carry-over were insignificant. Subsequently, the in vitro metabolism of PTU was assessed and UGT1A9 was identified as an important UGT isoform responsible for the glucuronidation of PTU. The information obtained from this study will facilitate future mechanistic investigation on the hepatoxicity of PTU and may optimize its clinical application.Keywords:propylthiouracil;propylthiouracil glucuronide;in vitro;human liver microsomes;UGT1A9;HPLC-MS/MS
研究领域:
药理学
·
分析化学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NUCLEIC ACIDS RESEARCH
·
2019
·Vol. 47
·期 19
·e119
·
IF 11.147
Chen Danping,Wang Yang,Mo Mingming,Zhang Junjie,Zhang Yanfei,Xu Yuzhi,Liu Si-Yang,Chen Jun,Ma Yingjun,Zhang Li,Dai Zong,Cai Chun,Zou Xiaoyong
The current methods for quantifying genome-wide 5-methylcytosine (5mC) oxides are still scarce, mostly restricted with two limitations: assay sensitivity is seriously compromised with cost, assay time and sample input; epigenetic information is irreproducible during polymerase chain reaction (PCR) amplification without bisulfite pretreatment. Here, we propose a novel Polymerization Retardation Isothermal Amplification (PRIA) strategy to directly amplify the minute differences between epigenetic bases and others by arranging DNA polymerase to repetitively pass large electron-withdrawing groups tagged 5mC-oxides. We demonstrate that low abundant 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxycytosine (5caC) in genomic DNA can be accurately quantified within 10 h with 100 ng sample input on a laboratory real-time quantitative PCR instrument, and even multiple samples can be analyzed simultaneously in microplates. The global levels of 5hmC and 5fC in mouse and human brain tissues, rat hippocampal neuronal tissue, mouse kidney tissue and mouse embryonic stem cells were quantified and the observations not only confirm the widespread presence of 5hmC and 5fC but also indicate their significant variation in different tissues and cells. The strategy is easily performed in almost all research and medical laboratories, and would provide the potential capability to other candidate modifications in nucleotides.
研究领域:
分子生物学
·
表观遗传学
·
基因组学
·
生物化学
·
医学诊断
✓ 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）