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101.
Non-small cell lung cancer (NSCLC) is a lethal non-immunogenic malignancy and proto-oncogene ROS-1 tyrosine kinase is one of its clinically relevant oncogenic markers. The ROS-1 inhibitor, crizotinib, demonstrated resistance due to the Gly2032Arg mutation. To curtail this resistance, researchers developed lorlatinib against the mutated kinase. In the present study, a receptor-ligand pharmacophore model exploiting the key features of lorlatinib binding with ROS-1 was exploited to identify inhibitors against the wild-type (WT) and the mutant (MT) kinase domain. The developed model was utilized to virtually screen the TimTec flavonoids database and the retrieved drug-like hits were subjected for docking with the WT and MT ROS-1 kinase. A total of 10 flavonoids displayed higher docking scores than lorlatinib. Subsequent molecular dynamics simulations of the acquired flavonoids with WT and MT ROS-1 revealed no steric clashes with the Arg2032 (MT ROS-1). The binding free energy calculations computed via molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) demonstrated one flavonoid (Hit) with better energy than lorlatinib in binding with WT and MT ROS-1. The Hit compound was observed to bind in the ROS-1 selectivity pocket comprised of residues from the β-3 sheet and DFG-motif. The identified Hit from this investigation could act as a potent WT and MT ROS-1 inhibitor. 相似文献
102.
gota Simon Adriana Smarandache Vicentiu Iancu Mihail Lucian Pascu 《Molecules (Basel, Switzerland)》2021,26(8)
The evolution of different antimicrobial drugs in terrestrial, microgravity and hypergravity conditions is presented within this review, in connection with their implementation during human space exploration. Drug stability is of utmost importance for applications in outer space. Instabilities may be radiation-induced or micro-/hypergravity produced. The antimicrobial agents used in space may have diminished effects not only due to the microgravity-induced weakened immune response of astronauts, but also due to the gravity and radiation-altered pathogens. In this context, the paper provides schemes and procedures to find reliable ways of fighting multiple drug resistance acquired by microorganisms. It shows that the role of multipurpose medicines modified at the molecular scale by optical methods in long-term space missions should be considered in more detail. Solutions to maintain drug stability, even in extreme environmental conditions, are also discussed, such as those that would be encountered during long-duration space exploratory missions. While the microgravity conditions may not be avoided in space, the suggested approaches deal with the radiation-induced modifications in humans, bacteria and medicines onboard, which may be fought by novel pharmaceutical formulation strategies along with radioprotective packaging and storage. 相似文献
103.
Pengcheng Li Jie Dai Yi Xu Qichao Ran Yi Gu 《Journal of polymer science. Part A, Polymer chemistry》2019,57(14):1587-1592
A difunctional benzoxazine (coPh‐apa) with a conjugated alkyne group is synthesized by the oxidative coupling reaction from a monocycle‐benzoxazine (Ph‐apa) containing an alkyne group. A model compound, 1,4‐diphenylbutadiyne (coPa), is used to study the curing reaction process of coPh‐apa by DSC, Fourier transform infrared spectroscopy, and 13C NMR, and the results suggest that the conjugated alkyne groups are involved in the crosslinking reaction via the trimerization reaction of the conjugated alkynyl groups and the Diels–Alder reaction. Furthermore, thermal properties of the polybenzoxazine are studied by dynamic thermomechanical analysis and thermogravimetric analysis. A glass‐transition temperature (Tgs) of as high as 412 °C and a char yield of 75.6% at 800 °C under nitrogen are obtained with the aid of the conjugated alkyne groups. Its excellent heat resistance dominates most thermosetting resins and will serve for heat shields. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1587–1592 相似文献
104.
Ariadna Lázaro Cristina Balcells Dr. Josefina Quirante Prof. Josefa Badia Prof. Laura Baldomà Dr. Jas S. Ward Prof. Kari Rissanen Dr. Mercè Font-Bardia Prof. Laura Rodríguez Dr. Margarita Crespo Prof. Marta Cascante 《Chemistry (Weinheim an der Bergstrasse, Germany)》2020,26(9):1947-1952
Platinum-based chemotherapy persists to be the only effective therapeutic option against a wide variety of tumours. Nevertheless, the acquisition of platinum resistance is utterly common, ultimately cornering conventional platinum drugs to only palliative in many patients. Thus, encountering alternatives that are both effective and non-cross-resistant is urgent. In this work, we report the synthesis, reduction studies, and luminescent properties of a series of cyclometallated (C,N,N′)PtIV compounds derived from amine–imine ligands, and their remarkable efficacy at the high nanomolar range and complete lack of cross-resistance, as an intrinsic property of the platinacycle, against multiplatinum-resistant colorectal cancer (CRC) and castration-resistant prostate cancer (CRPC) metastatic cell lines generated for this work. We have also determined that the compounds are effective and selective for a broader cancer panel, including breast and lung cancer. Additionally, selected compounds have been further evaluated, finding a shift in their antiproliferative mechanism towards more cytotoxic and less cytostatic than cisplatin against cancer cells, being also able to oxidize cysteine residues and inhibit topoisomerase II, thereby holding great promise as future improved alternatives to conventional platinum drugs. 相似文献
105.
106.
目的 探讨钙蛋白酶-10 基因(CAPN-10)单核苷酸多态性-19(SNP-19)与多囊卵巢综合征(PCOS)的相关性。
方法 采用聚合酶链反应- 限制性片段长度多态性(PCR-RFLP)技术,对107 例PCOS患者(PCOS 组)及111 例健康体检者(对照组)的CAPN-10 SNP-19 进行分析,并测定其性激素和生化指标。PCOS组再根据BMI与胰岛素抵抗(IR)稳态模型指数(HOMA-IR)分为肥胖组与非肥胖组、IR 组与非IR 组,分析CAPN-10 SNP-19 与其关系。结果 与对照组相比,PCOS 组BMI、空腹血糖(FPG)、TG、TC、LDL、黄体生成素(LH)、黄体生成素/ 卵泡刺激素(LH/FSH)、睾酮(T)均升高(均P<0.01)。PCOS 组CAPN-10 SNP-19 1等位基因及1/2基因型频率均高于对照组(均P<0.05);且CAPN-10 SNP-19 1/2基因型PCOS 发病风险较1/1、2/2 基因型增加约2倍(OR=1.9,95%CI=1.1~3.3,P<0.05)。CAPN-10 SNP-19 1、2等位基因频率PCOS 肥胖组与非肥胖组、IR 组与非IR组比较均无统
计学差异(均P>0.05);PCOS 肥胖组和IR组CAPN-10 SNP-19 1/2基因型频率分别高于非肥胖组和非IR 组,但差异均无统计学意义(均P>0.05)。结论 CAPN-10 SNP-19 与PCOS 遗传易感性有关,可能与PCOS 肥胖及IR 无关。 相似文献
107.
108.
Peng Zhang Wenzhe Wang Yingfang Zhou Gang Ruan Haiyang Yu Wenjuan Ji 《高分子科学杂志,A辑:纯化学与应用化学》2013,50(11-12):764-769
AbstractA novel cationic water-soluble monomer allyldimethylisooctylammonium bromide (ADIAB) containing a short-chain alkane was synthesized successfully. This monomer was copolymerized with acrylamide and sodium acrylate to produce hydrophobically modified polyacrylamide (HMPAM) using solution polymerization without surfactants. The structures of monomer ADIAB and HMPAM were characterized with infrared spectroscopy and nuclear magnetic resonance spectroscopy. Influence of preparation condition on viscosities of products was studied. The aqueous solution viscosity of the terpolymer was also investigated as functions of concentration, temperature and salinity. The results showed that when the temperature exceeds the 60?°C and NaCl concentration exceeds about 2000?mg/L, the temperature and salt tolerance characters of terpolymer were demonstrated. The enhanced oil recovery tests were initially carried out using homogeneous sandpack models. 相似文献
109.
Environmental stress cracking resistance (ESCR) is an important indicator of performance for high density polyethylene (HDPE) in structural and polymer pipe applications. The commonly used test for determining ESCR of HDPE can be time consuming and rather imprecise. A tensile strain hardening test was recently proposed to offer a faster way to characterize ESCR of polyethylene. In this paper, a practical approach is adopted whereby the test is extended to room temperature and shown to relate reliably to the ESCR of HDPE. Several HDPE resins (including pipe‐grade resins) are analyzed at strain rates of 0.5 mm/min and 7 mm/min to compare the effect of strain rate. Comparisons between the conventional ESCR test method and the strain hardening test show that strain hardening can be used to rank ESCR of HDPE in a reliable fashion. In our study the more direct measure of “hardening stiffness” is used to compare resins instead of strain hardening modulus. Because no true stress‐strain measurement is needed, this is a much simpler test method than other methods previously suggested. In addition, the use of the natural drawing ratio (NDR) as ESCR ranking indicator is examined. Results show that NDR can also be employed as a strain rate‐independent indicator of ESCR of HDPE. The test proposed herein is practical, simple and precise, and hence a more reliable indicator of ESCR performance of HDPE. 相似文献
110.
采用溶胶-浸渍法,以CuSO4为烧结助剂在碳纤维表面制得TiO2涂层。利用XRD、SEM和TEM分析了涂层相组成及形貌,通过静态等温氧化实验考察了涂层碳纤维抗氧化性能。结果表明:掺杂CuSO4制备TiO2涂层均匀完整致密,涂层相组成均为锐钛矿型TiO2,且涂层厚度从45 nm提高至185 nm;与普通TiO2涂层碳纤维相比,完全氧化温度从667 ℃上升到800 ℃,氧化活化能从118.390 kJ·mol-1提高到152.562 kJ·mol-1,CuSO4的掺杂大大提高了TiO2涂层碳纤维的抗氧化性能。 相似文献