JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 6.8
Yabing Xin,Can Xiao,Nan Wang,Huidan Wu,Wenjing Kang,Xuetao Chen,Chihong Liu,Qidong You,Zhengyu Jiang,Xiaoke Guo
Acute myeloid leukemia (AML) patients usually exhibit suboptimal responses after receiving single target drug therapy. Simultaneously targeting multiple oncogenic pathways is a promising strategy for cancer treatment. Herein, based on the synergistic antiproliferative capacity of the PIM inhibitor C28 and the HDAC inhibitor SAHA in MV4–11 cells, we developed a series of novel dual PIM/HDAC inhibitors. Among them, compound 22 exhibited potent antiproliferative activity in MV4–11 cells, along with robust inhibitory effects against both PIM1 and HDAC6. Flow cytometry analysis showed that 22 dose-dependently induced apoptosis in MV4–11 cells. Mechanistically, treatment with 22 remarkably induced the cleavage of PARP, thereby initiating apoptosis. Furthermore, 22 demonstrated significant anticancer efficacy (TGI = 81.3%; 50 mg/kg, QD) in the MV4–11 xenograft model without notable toxicity. In conclusion, our study established the therapeutic potential of dual PIM/HDAC inhibitors and provided a tool to elucidate synergistic mechanisms underlying the combined inhibition of these targets.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR LIQUIDS
·
2024
·
IF 5.3
Fei Gao,Peng Xu,Yan Zhang
During deep-water drilling operations, due to the conditions with low temperature and high pressure in the wellbore, methane hydrate can be easily formed in the presence of methane and plug the wellbore. In addition, the deep-water sediments are dominated by clay-silty with weak cementation, so well instability may be occurred due to clay hydration. In order to inhibit hydrate formation and clay hydration in deepwater drilling, a zwitterionic polymer AADV was synthesized through quaternary copolymerization of AM/AMPS/DMDAAV/VAC. The hydrate inhibition performance of AADV was evaluated in a high-pressure reactor chamber, and the results showed that AADV can delay the hydrate formation time from 330 min in pure water to 2204 min, indicating an excellent inhibition effect of hydrate formation. Meanwhile, 1 % AADV can significantly reduce the linear swelling rate of the calcium-based bentonite to 3.69 % for 10 h and increase the rolling recovery rate to 94.7 %, suggesting an excellent inhibition effect on clay hydration. The mechanism of dual-functional inhibition of AADV was further analyzed. The zwitterionic group in AADV and the hydrophilic amide group can strongly adsorb the water molecules through a strong hydration effect and the hydrogen bonding effect, respectively, which contributes to destroy the water molecules cage structure, and thus to suppress the hydrate formation. Besides, AADV can effectively obstruct mass transfer of methane molecules by increasing the viscosity of the aqueous phase and absorbing on the hydrate surface, leading to hydrate formation inhibition. For the inhibition of clay hydration, the SEM and XRD results proved that AADC inhibits the clay hydration through the film-forming effect. In addition, the contact angle of Na-Bent/AADC composite reached to 55.68° when the polymer concentration increased to 2 %, suggesting that the hydrophobicity of Na-Bent surface can be enhanced after AADC treatment. AADV can wrap around clay particles and form hydrophobic film through adsorption and intercalation, preventing the intrusion of external fluids and inhibiting clay hydration.
研究领域:
化学工程
·
石油工程
✓ 已验证
产品关联
DOI
高影响因子
Gas Science and Engineering
·
2024
·
IF 0
Jintang Wang,Bo Liao,Lei Liu,Longqiao Chen,Yaowei Huang,Ke Zhao,Xiaohui Sun,Kaihe Lv,Yuxuan Zheng,Jinsheng Sun
Based on the existing components of drilling fluids, the construction of a multi-component hydrate inhibitor system is essential for building a high-performance hydrate drilling fluid system and reducing production costs. The constant rate cooling method are performed to investigate the effect of different inhibitor systems on hydrate formation . The results indicate that thermodynamic inhibitors exhibit enhanced effectiveness in inhibiting hydrate formation at higher mass concentrations. In contrast, kinetic inhibitors demonstrate superior performance at lower mass concentrations, and their inhibitory efficacy does not scale up with concentration. Kinetic inhibitors can synergize with other components of the drilling fluid that have thermodynamic inhibitor effects. In particular, the ternary composite system has better synergistic effects compared to the binary composite system. It is of great significance for the construction of efficient hydrate drilling fluid systems in the future.
研究领域:
石油工程
·
化学工程
✓ 已验证
DOI
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
·
2025
·
IF 3
Xiaolu Wei,Guidan Ning,Huitong Ma,Yujiao Yin,Jianchun Ma,Liang Han,Danqi Chen,Zhongfeng Shi
At the heart of cancer pathology lies the dysregulated cell cycle, which is often driven by aberrant activities of the cell cycle regulating, cyclin-dependent kinases (CDKs). Efforts to harness the therapeutic potential of modulating CDK activities have led to the development of inhibitors with tailored CDK selectivity. However, uniformity in the methods used to evaluate CDK inhibitor selectivity has been lacking and consequently, direct comparison and interpretation of selectivity profiles determined under different assay conditions is difficult. Determination of the inhibition modalities crucial to profiling selectivity of a CDK inhibitor requires thorough kinetic analysis carried out under comparable assay conditions. In this study, we employed a streamlined series of in vitro assays for profiling CDK inhibitors wherein intrinsic inhibition constants and cellular binding parameters were measured by using strategically designed enzymatic inhibition and complementary biophysical assays. Our findings demonstrate the effectiveness of this strategy in determining and quantitatively analyzing the selectivity and inhibition modality of a set of representative CDK inhibitors towards the major oncogenic, cell cycle CDKs. In addition, the assay results provide insights into the inhibitor-target interactions that extend beyond potency and selectivity.
研究领域:
分子生物学
·
药理学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RARE METALS
·
2024
·
IF 9.6
Wang Wei-Wei,Huang Rui,Tao Yu,He Peng,Tuo Su-Xing,Bian Yu-Jian,Hu Rui-Ting,Yan Jun,Liang Yan-Jie,Zhang Wen-Chao
The electrochemical utilization of Zn anodes in aqueous batteries is hampered by the intricate and interconnected issues of Zn dendrite growth, H 2 evolution and Zn corrosion reactions. In this study, a multifunctional protective layer comprising MXene and graphitic carbon nitride (g-C 3 N 4 ) was constructed using a self-assembly strategy. The MXene/g-C 3 N 4 protective layer exhibited robust zincophilic characteristics, which facilitated a uniform distribution of the electric field and ensured a sufficient influx of Zn 2+ . This reduces the Zn 2+ nucleation barrier and prevents dendrite growth. In addition, the hydrophobic nature of the protective layer, coupled with its negative charge, can repel SO 4 2− and select water molecules from the electrolyte, which aids in mitigating corrosion and H 2 evolution. The symmetric Zn cell coated with the MXene/g-C 3 N 4 protective layer showed remarkable stability, achieving over 2000 h of reversible cycling at 1 mA·cm −2 . Furthermore, the MXene/g-C 3 N 4 -coated Zn anode paired with a sodium-doped V 2 O 5 cathode (NVO) exhibited enhanced cycling capability over 1500 cycles. Graphical Abstract
研究领域:
材料科学
·
电化学
·
能源存储
✓ 已验证
产品关联
DOI
高影响因子
FOOD CHEMISTRY
·
2017
·
IF 4.529
Kitty S.C. Tang,Izabela Konczak,Jian Zhao
The chemical identity and bioactivities of phenolic components of the Australian native herb Prostanthera rotundifolia were studied. Phenolic compounds were extracted with 80% (v/v) aqueous methanol and purified by liquid chromatography. The antioxidant capacity of the extract and its inhibiting activity against α-glucosidase, pancreatic lipase and hyaluronidase were determined. Phenolic compounds were identified by a combination of HPLC-PDA, LC-high resolution MS (LC-HRMS), LC-tandem MS (LC–MS/MS) and nuclear magnetic resonance (NMR) spectroscopy. Compared to spearmint, mint bush showed comparable antioxidant capacity, stronger inhibitory activity on pancreatic lipase and comparable and lower activity on α-glucosidase and hyaluronidase, respectively. Major compounds identified were verbascoside (48.8%), 4-methoxycinnamic acid (36.4%), p -coumaric acid glucose ester (9.2%) and 1- O -β- d -glucopyranosyl sinapate (5.6%), while caffeic acid, p -coumaric acid, hesperidin and naringenin were present in trace quantities. 4-Methoxycinnamic acid, p -coumaric acid glucose ester and 1- O -β- d -glucopyranosyl sinapate were identified for the first time in the genus of Prostanthera .
研究领域:
植物化学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PROGRESS IN ORGANIC COATINGS
·
2024
·
IF 6.5
Mustehsin Ali,Hongwei Shi,Faheem Jan,Sharjeel Ahmed,Yingwei Song,En-Hou Han
Ti 3 C 2 T x nanosheets, emerging as revolutionary 2D nanomaterials, have sparked interest in advanced applications due to their thin-layered architecture and promise as innovative nanofillers for a variety of applications. To address the oxidation and stacking of Ti 3 C 2 T x nanosheets with the polymer, a novel multifunctional Ti 3 C 2 T x -based nanocomposite is engineered by an etching method. The Ti 3 C 2 T x surface is functionalized with 3-aminopropyltriethoxysilane (APTES), and attapulgite (ATP) is implanted on the NH 2 -Ti 3 C 2 T x interface to lower the cohesive energy between nanosheets. The novel self-healing epoxy films were achieved by encapsulating self-healing components ((8-hydroxyquinoline (8-HQ) + 2-mercaptobenzothiazole (MBT)) in the ATP-based NH 2 -Ti 3 C 2 T x nanocomposite (AMQM). Inhibited AA2024-T3 surface revealed hydrophobic nature, whereas the pH sensitive coatings exhibited strong adherence to the substrate and improved compatibility and mechanical strength. The impedance of artificially scratched epoxy film rose from 0.073 M Ω cm 2 to 0.198 M Ω cm 2 (after 12 h) and from 0.027 M Ω cm 2 to 2.189 M Ω cm 2 (after 96 h) in comparison with the control samples. Simulations depict the presence of hydrogen bonds between the inhibitors and the 2024-T3 alloy, as well as twice the adsorption energy compared to the individual inhibitors. Therefore, a novel pH-sensitive self-healing coating offers a synergistic approach for promising corrosion suppression.
研究领域:
材料科学
·
化学工程
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2017
·
IF 2.714
Xinliang Li,Guancheng Jiang,Lili Yang,Shuanglei Peng
In order to develop a biodegradable and efficient shale inhibitor, gelatin, a biodegradable amino polymer, was introduced as a potential shale inhibitor. The inhibitive properties were evaluated by linear swelling test, hot-rolling recovery test and montmorillonite (MMT) plate soaking test. The results showed that the inhibition of gelatin was better than other common inhibitors. The inhibitive mechanism of gelatin was also investigated via a variety of characterization methods. First of all, gelatin was adsorbed on MMT particles through electrostatic interactions and hydrogen bonds. Then, the negative charge on MMT particles was neutralized and the double electrical layers were suppressed. For the adsorbed gelatin molecules, only a few molecules entered the interlayer space and expelled water. Meanwhile, the main part of gelatin was strongly adsorbed on the surface of MMT particles and formed a polymer film, which made clay surface more hydrophobic. Thus, the polymer formed an effective shield to prevent the invasion of water. Finally, the MMT layers were compressed together in a form of thicker and larger agglomerations and the hydration was well inhibited.
研究领域:
石油工程
·
材料科学
✓ 已验证
DOI
高影响因子
JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY
·
2023
·
IF 10.9
Yunfei Shen,Yi Liu,Kaisheng Sun,Tiantian Gu,Gang Wang,Yue Yang,Jianxiang Pang,Yang Zheng,Xiaodong Yang,Long Chen
Dendrites growth, chemical corrosion, and hydrogen evolution reaction (HER) on zinc anodes are the main barriers for the development of aqueous zinc-ion batteries (AZIBs). Constructing interfacial protective layer is an effective way to alleviate the side reactions on the anodes. Herein, Cu/Ti 3 C 2 Cl 2 MXene (CMX) with high zincophilic and hydrophobic property is prepared by the lewis molten salts etching method, and the CMX interface protection layer is constructed by a simple spin coating. The CMX coating layer can provide abundant nucleation sites and uniformize the charge distribution through the zincophilic Ti 3 C 2 Cl 2 MXene matrix, leading to homogenous Zn deposition. In addition, the hydrophobic coating contained anti-corrosive Cu nanoparticles can prevent the Zn anode from the electrolyte, beneficial for suppressing the chemical corrosion and HER. Therefore, the stable and reversible Zn plating/stripping is achieved for the Zn anode coated by the CMX, which exhibits the lifespan of over 1400 h at 0.5 mA cm −2 , and even can steadily run for 700 h with 65 mV at 10 mA cm −2 . Furthermore, CMX@Zn shows a high coulombic efficiency of over 100% for 3800 cycles, which indicates that the CMX@Zn electrode has excellent stability and reversibility of Zn stripping/plating. The full batteries assembled with ZnCoMnO/C (ZCM) cathodes also exhibits higher capacity (450.6 mAh g −1 at 0.1 A g −1 ) and cycle stability (capacity retention of 70% after 1500 cycles). This work enhanced the lifespan of AZIBs and broaden the research of multifunctional coating layer to other secondary batteries based on metal anodes.
研究领域:
材料科学
·
电化学
·
能源存储
✓ 已验证
DOI
高影响因子
THERMOCHIMICA ACTA
·
2025
·
IF 3.5
Jiajun Guo,Wentao Ji,Yabei Xu,Zhitao Chen,Yang Su,Yan Wang
This paper takes the typical thermally unstable azo compound AIBN as the research object. For the key free radicals in its explosive chain reaction, two inhibitors and two target inhibitory additives were selected. Through a 20-liter spherical test device and gas-phase product analysis, the inhibitory effect of the target inhibitory additives on the explosive chain reaction was derived. The inhibition mechanism was expounded from both physical and chemical inhibition aspects through ARC experiments.The experimental results show that AIBN has very high risk of explosion and severity,. However, the compounding of DW with FAS and KI can effectively inhibit the explosion pressure and achieve complete explosion suppression, while also inhibiting the generation of toxic gases. The ARC studies discovered that FAS and KI can increase the adiabatic temperature of the thermal decomposition process of AIBN and significantly reduce the apparent activation energy of the reaction to achieve the effect of inertia.
研究领域:
化学安全
·
化学动力学
·
热分析
·
防爆技术
·
气相化学
✓ 已验证
产品关联
DOI
高影响因子
CHEMISTRY & BIODIVERSITY
·
2021
·Vol. 19
·期 1
·e202100740
·
IF 2.408
Xiang Liu,Jinqiu Rao,Kai Wang,Meijun Wang,Tie Yao,Feng Qiu
Many stilbene glycosides can alleviate skin hyperpigmentation due to their inhibitory effect on tyrosinase. Mulberrosides in Morus alba L. are stilbene glycosides. In the present study, the inhibition of tyrosinase by five mulberrosides (S1–5), isolated from Morus alba L. was investigated and compared, and the inhibitory mechanism was explored. These five mulberrosides exhibited obvious inhibitory effects on tyrosinase only in a concentration-dependent manner, without time-dependence, indicating that they are reversible inhibitors of tyrosinase. S2, S1 and S5 inhibited tyrosinase activity with IC 50 values of 28.93, 75.94 and 151.72 μM, respectively, and were more active than kojic acid (IC 50 =169.13 μM). Kinetic studies revealed that S1, S2 and S4 were competitive inhibitors, while S3 and S5 were mixed inhibitors. Analysis of the fluorescent spectra showed that mulberrosides S1, S2 and S4 quenched the intrinsic fluorescence intensity of tyrosinase. A molecular docking study indicated that the interaction of tyrosinase with mulberrosides was reflected by compound scores as follows: S2>S5>S1>S3/S4>kojic acid, and hydroxy groups in the side chain of mulberrosides may play a crucial role in the binding of the enzyme. Our results suggest that mulberrosides in Morus alba L. could be further developed as whitening agents for enhanced performance against hyperpigmentation. Graphical
研究领域:
植物化学
·
生物化学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CORROSION SCIENCE
·
2022
·
IF 7.72
Yanan Cui,Tao Zhang,Fuhui Wang
The effect of inhibitors on the corrosion behavior of AZ91D magnesium (Mg) alloy was investigated via a combination of experimental and computational approaches. A new inhibition mechanism was proposed that the nucleation of corrosion products affected by inhibitor. The Mg(OH) 2 embryos carry positive charges during the metal dissolution process because the pH is lower than the isoelectric point. The positively charged embryos suppress the crystal nucleation, indicating that the inhibitor with negative charges can adsorb on the embryos, resulting in the acceleration of the embryo growths. Consequently, a dense corrosion product film and superior inhibition efficiency were obtained.
研究领域:
材料科学
·
电化学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）