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41.
Anticonvulsant Activity of Enantiomeric N‐trans‐Cinnamoyl Derivatives of 2‐Aminopropan‐1‐ols and 2‐Aminobutan‐1‐ols 下载免费PDF全文
Agnieszka Gunia‐Krzyżak Ewa Żesławska Wojciech Nitek Justyna Popiół Henryk Marona 《Chirality》2016,28(6):482-488
Epilepsy, one of the most frequent neurological disorders, is still insufficiently treated in about 30% of patients. As a consequence, identification of novel anticonvulsant agents is an important issue in medicinal chemistry. In the present article we report synthesis, physicochemical, and pharmacological evaluation of N‐trans‐cinnamoyl derivatives of R and S‐2‐aminopropan‐1‐ol, as well as R and S‐2‐aminobutan‐1‐ol. The structures were confirmed by spectroscopy and for derivatives of 2‐aminopropan‐1‐ols the configuration was evaluated by means of crystallography. The investigated compounds were tested in rodent models of seizures: maximal electroshock (MES) and subcutaneous pentetrazol test (scPTZ), and also in a rodent model of epileptogenesis: pilocarpine‐induced status prevention. Additionally, derivatives of 2‐aminopropan‐1‐ols were tested in benzodiazepine‐resistant electrographic status epilepticus rat model as well as in vitro for inhibition of isoenzymes of cytochrome P450. All of the tested compounds showed promising anticonvulsant activity in MES. For R(–)‐(2E)‐N‐(1‐hydroxypropan‐2‐yl)‐3‐phenylprop‐2‐enamide pharmacological parameters were found as follows: ED50 = 76.7 (68.2–81.3) mg/kg (MES, mice i.p., time = 0.5 h), ED50 = 127.2 (102.1–157.9) mg/kg (scPTZ, mice i.p., time = 0.25 h), TD50 = 208.3 (151.4–230.6) mg/kg (rotarod, mice i.p., time = 0.25 h). Evaluation in pilocarpine status prevention proved that all of the reported compounds reduced spontaneous seizure activity and act as antiepileptogenic agents. Both enantiomers of 2‐aminopropan‐1‐ols did not influence cytochrome P450 isoenzymes activity in vitro and are likely not to interact with CYP substrates in vivo. Chirality 28:482–488, 2016. © 2016 Wiley Periodicals, Inc. 相似文献
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Wojciech Lipinski Joanna Wasko Malgorzata Walczak Justyna Fraczyk Zbigniew J. Kaminski Krystian Galecki Zbigniew Draczynski Izabella Krucinska Marta Kaminska Beata Kolesinska 《化学与生物多样性》2019,16(11)
The aim of the study was the assessment of the ability of short peptides to form aggregates under physiological conditions. The dipeptides studied were derived from different aromatic amino acids (heteroaromatic peptides). Tripeptides were obtained from two distinct aromatic amino acids and cysteine or methionine residue in the C‐terminal, N‐terminal, or central position. The ability of the peptides to form fibrous aggregates under physiological conditions was evaluated using three independent methods: the Congo Red assay, the Thioflavin T assay, and microscopic examinations using normal and polarized light. Materials potentially useful for regenerative medicine were selected based on their cytotoxicity to the endothelial cell line EA.hy 926 and physicochemical properties of films formed by peptides. The required parameters of biocompatibility were fulfilled by H?PheCysTrp?OH, H?PheCysTyr?OH, H?PheTyrMet?OH, and H?TrpTyr?OH. 相似文献
44.
Liucija Weselik Ewa Majchrzak Matthew Ibbs Adam Lewandowski Andrzej Marszałek Piotr Machczyński Wojciech Golusiński 《Reports of Practical Oncology and Radiotherapy》2019,24(5):443-449
AimThe aim of the study was to assess the accuracy of radiological diagnosis of laryngeal cartilage infiltration by histopathological examination of laryngeal specimen after total laryngectomy.BackgroundDespite the development of new medical technologies and significant clinical advances allowing early diagnosis and treatment of laryngeal cancer, mortality is still on the rise. Neoplastic infiltration of the laryngeal cartilages is the most common source of error in the assessment of cancer staging. Furthermore, cartilage invasion is listed as a contraindication to partial surgical techniques as well as radiotherapy.Materials and methodsThe study was carried out on 21 larynges following total laryngectomy. Before taking the decision to perform surgery, high-resolution CT scans were performed in all cases. An extended histopathological examination was conducted using a unique vertical cross-section of the whole larynx.ResultsPathology reported 2 cases of arytenoid cartilage invasion, 5 cases of cricoid cartilage invasion, 12 cases of thyroid cartilage penetration, 1 case of internal cortex invasion and 9 cases of extra-laryngeal spread. CT imaging identified 8 of 13 cases (61.5%) of pathologically proven invasion of thyroid cartilage and only 2 cases (2/9, 22%) of extra-laryngeal spread. According to CT results, arytenoid cartilage invasion was correctly identified in 2 cases, cricoid cartilage invasion in 4 (4/5, 80%). The positive predictive values for thyroid, cricoid and arytenoid cartilage invasion and penetration were 80%, 66.7% and 50%, respectively. In case of pre-laryngeal spread the positive predictive value was 100%.ConclusionDespite increasingly advanced methods involved in the diagnosis of laryngeal cancer, many discrepancies may be observed between the radiological and histopathological assessments. CT imaging has limitations especially in thyroid cartilage penetration and extra-laryngeal spread assessment in advanced laryngeal cancer cases. An extended histopathological examination, involving vertical cross-sections of the whole larynx is a very precise study that allows a precise determination of local cancer staging (T). 相似文献
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Michael Jakob Rupar Pawel Golusinski Wojciech Golusinski Michal M. Masternak 《Reports of Practical Oncology and Radiotherapy》2019,24(6):544-550
Human Papillomavirus (HPV) remains one of the most commonly contracted sexually transmitted diseases around the world. There are a multitude of HPV types, some of which may never present any symptoms. Others, however, are considered high-risk types, which increase the chance of the person infected to develop cancer. In recent years, the utilization of nanotechnology has allowed researchers to employ and explore the use of nanoparticles in immunotherapies.The new nanoparticle frontier has opened many doors in this area of research as a form of prevention, diagnosis, and treatment in cancers resulting from HPV. This review will provide a brief background of HPV, its relationship to head and neck cancer (HNC) and present some insight into the field of immunotherapeutic nanoparticles. 相似文献
46.
This paper presents an ab initio quantum chemical investigation of the geometrical structures and the non-linear optical properties (NLO) of three structural isomers of pyridinium N-phenolate betaine dye. The ground state geometrical parameters and the first-order hyperpolarizabilities were calculated using the Hartree-Fock (HF) as well as the second-order perturbation Møller-Pleset (MP2) method with the 6–31G, 6–31G(d), 6–31G(d,p), 6–31+G(d), 6–31++G(d,p), 6–311+G(d), aug-cc-PVDZ and the recently developed Z3PolX basis sets. Moreover, the first-order hyperpolarizability was calculated at the coupled cluster singles and doubles (CCSD/6–31+G(d)) level of theory. The analysis of the results of calculations for the investigated isomers indicates that there are important differences in their NLO activities. Additionally, it was shown that Z3PolX basis set works reasonable well for betaine dyes. Figure
The molecules investigated in the present study. (Figure prepared using Mercury 1.5.) 相似文献
47.
Gaucher disease is a lysosomal storage disorder caused by deficiency of human acid β-glucosidase. Recent x-ray structural
elucidation of the enzyme alone and in the presence of its inhibitor was done, which provided an excellent template for further
studies on the binding of substrate, product and inhibitor. To draw correlations between the clinical manifestation of the
disease driven by point mutations, L444P and L444R, and the placement and function of putative S-binding sites, the presented
theoretical studies were undertaken, which comprised of molecular dynamics and molecular docking methods. The obtained results
indicate the D443 and D445 residues as extremely important for physiological functionality of an enzyme. They also show, although
indirectly, that binding of the substrate is influenced by an interplay of E235 and E334 residues, constituting putative substrate
binding site, and the region flanked by D435 and D445 residues.
Figure The binding of an arbitrarily chosen structure of glucosylceramide (A), conduritol-β-epoxide (B), glucose (C) to the active
site D443/D445 (A1, B1, C1) and E320/E340 (A2, B2, C2) of the wild-type structure of human acid-β-glucosidase. A1, B1, C1
blue mask represents the residues D443-D445; red mask represents the residue D444; A2, B2, C2 blue mask represents loop1 (Ser345-Glu349) and loop2 (Val394-Asp399), whereas red mask the residues E235 and 340 相似文献
48.
Harańczyk Michał Konieczyńska Małgorzata Płazak Wojciech 《Sleep and biological rhythms》2022,20(1):65-72
Sleep and Biological Rhythms - Obstructive sleep apnea syndrome (OSAS) is considered to be an important predisposing factor for cardiovascular diseases. The main objective of this study was to... 相似文献
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F. William Sunderman Alison H. Varghese Olga S. Kroftova Svetlana Grbacivankovic Jaromir Kotyza Arun K. Datta Milton Davis Wojciech Bal Kazimierz S. Kasprzak 《Molecular reproduction and development》1996,44(4):507-524
A Ni(II)-binding serpin, pNiXA, is abundant in Xenopus oocytes and embryos. Kinetic assays show that purified pNiXa strongly inhibits bovine α-chymotrypsin (K1 = 3 mM), weakly inhibits porcine elastase (K1 = 0.5 μM), and does not inhibit bovine trypsin. The reversible, slow-binding inhibition of α-chymotrypsin by pNiXa is unaffected by Ni(II). Ovochymase in egg exudates is inhibited by pNiXa, but to a limited extent, even at high pNiXa concentrations. An octadecapeptide that models the His-rich domain (-HRHRHEQQGHHDSAKHGH-) of pNiXa forms six-coordinate, octahedral Ni(II)-complexes when the N-terminus is acetylated, and a square-planar Ni(II)-complex when the N-terminus is unblocked. Spectroscopy reveals two distinct types of octahedral Ni(II)-coordination to the N-acetylated octadecapeptide, involving, respectively, 3–4 and 5–6 imidazole nitrogens; the octadecapeptide undergoes partial, reversible precipitation in pH-and Ni(II)-dependent fashion, suggesting an insoluble, Ni(II)-coupled (Hx)n-dimer. Such (Hx)n-peptide interaction is confirmed by an enzyme-linked biotin-avidin assay with N-biotin-KHRHRHE-amide and N-acetyl-KHRHRHE-resin beads, which become coupled after adding Ni(II) or Zn(II). H2O2 oxidation of 2′-deoxyguanosine to mutagenic 8-hydroxy-2′deoxyguanosine is enhanced by the octahedral Ni(II)-octadecapeptide complex, although the effect is more intense with the square-planar Ni(II) octadecapeptide complex. Immunoperoxidase staining of whole mounts wish pNiXa antibody shows that pNiXa is distributed throughout gastrula-stage embryos and is localized during organogenesis in the brain, eye, spinal cord, myotomes, craniofacial tissues, and other sites of Ni(II) induced anomalies. Patterns of pNiXa staining are similar in controls and Ni(II)-exposed embryos. Binding of Ni(II) to pNiXa may cause embryotoxicity by enhancing oxidative reactions that produce tissue injury and genotoxicity. Although the natural target proteinases for pNiXa inhibition have not been established, pNiXa may be an important regulator of proteolysis during embryonic development. © 1996 Wiley-Liss, Inc. 相似文献