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排序方式: 共有1746条查询结果,搜索用时 46 毫秒
91.
《Journal of Saudi Chemical Society》2022,26(6):101539
The efficacy of most marketed antimalarial drugs has been compromised by the development of parasite resistance, underscoring an urgent need to find new drugs with new mechanisms of action. This article describes the synthesis and the in vitro antimalarial profiling of antifolate P218 analogues, by exploring a bioisosteric replacement of the carboxylic group by a phosphinic moiety as well as structural isomerization of P218. The detailed synthetic route employed to access the title compounds is described. The listed compounds exhibited low antimalarial activity against drug-resistant strains of P. falciparum including chloroquine-resistant W2. 相似文献
92.
Jiaming Zhang Yu Zhang Xiaoyu Liu Xiaolan Xu Yingchao Li Tianhong Zhang 《Journal of separation science》2022,45(4):968-975
Cinnarizine is a weak base, which can produce supersaturation and precipitation during gastrointestinal transit, affecting its absorption in vivo. Therefore, it is necessary to investigate whether the oral bioavailability of cinnarizine can be improved after co-administration with precipitation inhibitors or not. In order to evaluate the pharmacokinetic behavior of cinnarizine in rats, a simple, rapid, sensitive, and environmentally friendly supercritical fluid chromatography-tandem mass spectrometric method was established and validated. In this method, flunarizine, a structural analogue of cinnarizine, was selected as the internal standard, and cinnarizine was extracted from rat plasma using evaporation-free liquid–liquid extraction method. The analytes were separated on a Torus 1-AA column (3.0 mm × 100 mm, 1.7 μm) within 2.0 min, using a gradient elution procedure. The transitions of cinnarizine and flunarizine were m/z 369.1 → 167.1 and m/z 405.1 → 203.1, respectively. Cinnarizine showed good linear correlation in the range of 1–500 ng/ml with a lower limit of quantification of 1 ng/ml. The intra- and interday precision and accuracy of all quality control samples were within ±15%. This high-throughput, accurate, sensitive, and reproducible method has been successfully applied to study the effects of the precipitation inhibitor cinnarizine on the pharmacokinetics in rats. 相似文献
93.
以2-巯基苯并噻唑(2-MBT)、 苯并三氮唑(BTA)和苯氧基乙醇(MSDS)作为缓蚀剂, 研究了其加入在酸性蚀刻液后对PCB厚铜线路的缓蚀效果。通过接触角测试、电化学测试和蚀刻因子得出缓蚀状态,并结合扫描电子显微镜观察铜表面形貌。通过分子动力学计算和量子化学模拟分析缓蚀剂在铜表面的吸附机理。结果表明,2-MBT + MSDS与BTA + MSDS的分子结构可有效地平行吸附在铜表面,且吸附能高于单一缓蚀剂。加入了2-MBT + MSDS的蚀刻液,对厚度约为33 μm铜线路进行刻蚀,铜线路的蚀刻因子提高到6.59,可有效应用于PCB厚铜线路制作。 相似文献
94.
《Arabian Journal of Chemistry》2022,15(2):103573
Natural-based corrosion inhibitors have gained great research interest thanks to their low cost and higher performance. In this work, the chemical composition of the methanolic extract of Ammi visnaga umbels (AVU) was evaluated by gas chromatography (GC) coupled with mass spectrometry (MS) and applied for corrosion inhibition of carbon steel (CS) in 1.0 mol/L HCl using chemical and electrochemical techniques along with scanning electron microscope (SEM) and theoretical calculations. A total of 46 compounds were identified, representing 89.89% of the overall chemical composition of AVU extract, including Edulisin III (72.88%), Binapacryl (4.32%), Khellin (1.97%), and Visnagin (1.65%). Chemical (Weight loss) and electrochemical (potentiodynamic polarization curves (PPC), and electrochemical impedance spectroscopy (EIS)) techniques revealed that investigated extract can be used as an effective corrosion inhibitor for carbon steel in 1.0 mol/L HCl solution. At a low dose of 700 ppm, the inhibitory action of AVU extract reached an inhibition efficiency of 84 percent. According to polarization tests, the investigated extract worked as a mixed inhibitor, protecting cathodic and anodic corrosion reactions. The EIS test showed that upon the addition of AVU extract to HCl solution, the polarization resistance increased while the double layer decreased. SEM images showed a protected CS surface in the inhibited solution. Quantum chemical calculations by Density Functional Theory (DFT) for the main components confirmed the major role of heteroatoms and aromatic rings as adsorption sites. Molecular dynamics (MD) simulation was used to study the adsorption configuration of the main components on the Fe(1 1 0) surface. Outcomes from this study further confirmed the significant advantage of using plant-based corrosion inhibitors for protecting metals and alloys. 相似文献
95.
Polyphenolic and Terpenoids are potent natural antiparasitic compounds. This study aimed to identify new drug against Leishmania parasites, leishmaniasis’s causal agent. A new in silico analysis was accomplished using molecular docking, with the Autodock vina program, to find the binding affinity of two important phytochemical compounds, Masticadienonic acid and the 3-Methoxycarpachromene, towards the trypanothione reductase as target drugs, responsible for the defense mechanism against oxidative stress and virulence of these parasites. There were exciting and new positive results: the molecular docking results show as elective binding profile for ligands inside the active site of this crucial enzyme. The ADMET study suggests that the 3-Methoxycarpachromene has the highest probability of human intestinal absorption. Through this work, 3-Methoxycarpachromene and Masticadienonic acid are shown to be potentially significant in drug discovery, especially in treating leishmaniasis. Hence, drug development should be completed with promising results. 相似文献
96.
Silvie Rimpelov Michal Kol Hynek Strnad Tom Ruml Libor Vítek Helena Gbelcov 《Molecules (Basel, Switzerland)》2021,26(12)
Statins have been widely used for the treatment of hypercholesterolemia due to their ability to inhibit HMG-CoA reductase, the rate-limiting enzyme of de novo cholesterol synthesis, via the so-called mevalonate pathway. However, their inhibitory action also causes depletion of downstream intermediates of the pathway, resulting in the pleiotropic effects of statins, including the beneficial impact in the treatment of cancer. In our study, we compared the effect of all eight existing statins on the expression of genes, the products of which are implicated in cancer inhibition and suggested the molecular mechanisms of their action in epigenetic and posttranslational regulation, and in cell-cycle arrest, death, migration, or invasion of the cancer cells. 相似文献
97.
Elizaveta D. Gladkova Arina A. Chepanova Ekaterina S. Ilina Alexandra L. Zakharenko Jhannes Reynisson Olga A. Luzina Konstantin P. Volcho Olga I. Lavrik Nariman F. Salakhutdinov 《Molecules (Basel, Switzerland)》2021,26(7)
A new type of berberine derivatives was obtained by the reaction of berberrubine with aliphatic sulfonyl chlorides. The new polycyclic compounds have a sultone ring condensed to C and D rings of a protoberberine core. The reaction conditions were developed to facilitate the formation of sultones with high yields without by-product formation. Thus, it was shown that the order of addition of reagents affects the composition of the reaction products: when sulfochlorides are added to berberrubine, their corresponding 9-O-sulfonates are predominantly formed; when berberrubine is added to pre-generated sulfenes, sultones are the only products. The reaction was shown to proceed stereo-selectively and the cycle configuration was confirmed by 2D NMR spectroscopy. The inhibitory activity of the synthesized sultones and their 12-brominated analogs against the DNA-repair enzyme tyrosyl-DNA phosphodiesterase 1 (Tdp1), an important target for a potential antitumor therapy, was studied. All derivatives were active in the micromolar and submicromolar range, in contrast to the acyclic analogs and 9-O-sulfonates, which were inactive. The significance of the sultone cycle and bromine substituent in binding with the enzyme was confirmed using molecular modeling. The active inhibitors are mostly non-toxic to the HeLa cancer cell line, and several ligands show synergy with topotecan, a topoisomerase 1 poison in clinical use. Thus, novel berberine derivatives can be considered as candidates for adjuvant therapy against cancer. 相似文献
98.
Xiao-Qiang Jiang Shi-Quan Chen Yan-Fei Liu Xin-Guang Pan Dan Chen Shi-Fan Wang 《Molecules (Basel, Switzerland)》2021,26(7)
Solvothermal synthesis of multiple dihydropyrimidinones at a time has been developed in inexpensive and green bio-based solvent lactic acid without any additional catalysts or additives. By this method, thirty new dihydropyrimidinone derivatives were synthesized in two batches and characterized. All of the compounds were screened by Eg5 motor protein ATPase assay, and the positive compounds were tested against the Caco-2 cell line, HeLa cell line, L929 cell line and T24 cell line in vitro. Among them, compound C9 exhibited the best inhibitory activity against motor protein ATPase with an IC50 value of 30.25 μM and significant cytotoxic activity in the micromolar range against the cells above. The Lineweaver–Burk plot revealed that compound C9 was a mixed-type Eg5 inhibitor. A molecular modeling study using the Discovery Studio program was performed, where compound C9 exhibited good binding interaction with Eg5 motor protein ATPase, and this was consistent with the attained experimental results. 相似文献
99.
Saira Hussain Ata ur Rehman David J. Luckett Syed Muhammad Saqlan Naqvi Christopher L. Blanchard 《Molecules (Basel, Switzerland)》2021,26(7)
Valorization of vegetable oil waste residues is gaining importance due to their high protein and polyphenol contents. Protease inhibitors (PIs), proteins from these abundantly available waste residues, have recently gained importance in treating chronic diseases. This research aimed to use canola meal of genetically diverse Brassica napus genotypes, BLN-3347 and Rivette, to identify PIs with diverse functionalities in therapeutic and pharmacological applications. The canola meal PI purification steps involved: native PAGE and trypsin inhibition activity, followed by ammonium sulfate fractionation, anion exchange, gel filtration, and reverse-phase chromatography. The purified PI preparations were characterized using SDS-PAGE, isoelectric focusing (IEF), and N terminal sequencing. SDS-PAGE analysis of PI preparations under native reducing and nonreducing conditions revealed three polymorphic PIs in each genotype. The corresponding IEF of the genotype BLN-3347, exhibited three acidic isoforms with isoelectric points (pI) of 4.6, 4.0, and 3.9, while Rivette possessed three isoforms, exhibiting two basic forms of pI 8.65 and 9.9, and one acidic of pI 6.55. Purified PI preparations from both the genotypes displayed dipeptidyl peptidase-IV (DPP-IV) and angiotensin-converting enzyme (ACE) inhibition activities; the BLN-3347 PI preparation exhibited a strong inhibitory effect with lower IC50 values (DPP-IV 37.42 µg/mL; ACE 129 µg/mL) than that from Rivette (DPP-IV 67.97 µg/mL; ACE 376.2 µg/mL). In addition to potential human therapy, these highly polymorphic PIs, which can inhibit damaging serine proteases secreted by canola plant pathogens, have the potential to be used by canola plant breeders to seek qualitative trait locus (QTLs) linked to genes conferring resistance to canola diseases. 相似文献
100.
Eon-Joo Roh 《Molecules (Basel, Switzerland)》2021,26(8)
In this study, a series of coumarin derivatives were synthesized and their inhibitory effects on the activity of mushroom tyrosinase were evaluated. As a result of measuring the inhibition of tyrosinase activity of these derivatives, the compounds 3e (1.05 μM), 3f (0.83 μM), 3h (0.85 μM), 3i (1.05 μM), and 3k (0.67 μM) of the geranyloxycoumarin derivatives were highly active at a concentration of 0.8%. The geranyloxycoumarin derivatives exhibited better activity than the hydroxycoumarin derivatives. Among the geranyloxycoumarin derivatives, compound 3k was two times more active than arbutin, a positive control, at a concentration of 0.4%. The above results suggest that geranyloxycoumarin derivatives have great potential for application as functional cosmetic ingredients with tyrosinase-inhibiting activity. 相似文献