17 research outputs found
Synthesis and Determination of Physicochemical Properties of New 3-(4-Arylpiperazin-1-yl)-2-hydroxypropyl 4-Alkoxyethoxybenzoates
Nine new dihydrochloride salts of 3-(4-arylpiperazin-1-yl)-2-hydroxypropyl 4-alkoxyethoxybenzoates were designed and synthesized. The physicochemical properties such as lipophilicity index (log kw) and dissociation constant (pKa) were experimentally determined and compared to the software calculated data. The lipophilicity index was determined by means of reversed-phase high performance liquid chromatography (RP-HPLC). The pKa values were determined by means of capillary zone electrophoresis. The “drug-likeness” properties according to the Lipinski Rule of Five and prediction of possible blood–brain barrier penetration were computed and discussed
Characterization of sensitivity of optical fiber cables to acoustic vibrations
Abstract Fiber optic infrastructure is essential in the transmission of data of all kinds, both for the long haul and shorter distances in cities. Optical fibers are also preferred for data infrastructures inside buildings, especially in highly secured organizations and government facilities. This paper focuses on a reference measurement and analysis of optical fiber cables sensitivity to acoustic waves. Measurement was carried out in an anechoic chamber to ensure stable conditions of acoustic pressure in the range from 20Â Hz to 20Â kHz. The frequency response, the signal-to-noise ratio per frequency, and the Speech Transmission Index are evaluated for various types of optical fiber cables and different ceiling tiles, followed by their comparison. The influence of the means of fixing the cable is also studied. The results prove that optical fiber-based infrastructure in buildings can be exploited as a sensitive microphone
Synthesis and Characterization of New 3-(4-Arylpiperazin-1-yl)-2-hydroxypropyl 4-Propoxybenzoates and Their Hydrochloride Salts
Five new 3-(4-arylpiperazin-1-yl)-2-hydroxypropyl 4-propoxybenzoates were designed and synthesized as potential dual antihypertensive agents. The compounds were prepared as free bases and subsequently transformed to hydrochloride salts. The position of protonation of nitrogen atoms in the piperazine ring of hydrochloride salts was determined by means of 13C-CP/MAS and 15N-CP/MAS NMR and IR spectroscopy. Using these solid-state analytical techniques, it was found that both nitrogen atoms were protonated when excess hydrogen chloride was used for preparation of salts. On the other hand, when the equimolar amount of hydrogen chloride was used, piperazine nitrogen substituted by aryl was protonated
Synthesis, Analysis, Cholinesterase-Inhibiting Activity and Molecular Modelling Studies of 3-(Dialkylamino)-2-hydroxypropyl 4-[(Alkoxy-carbonyl)amino]benzoates and Their Quaternary Ammonium Salts
Tertiary amines 3-(dialkylamino)-2-hydroxypropyl 4-[(alkoxycarbonyl)amino]benzoates and their quaternary ammonium salts were synthesized. The final step of synthesis of quaternary ammonium salts was carried out by microwave-assisted synthesis. Software-calculated data provided the background needed to compare fifteen new resulting compounds by their physicochemical properties. The acid dissociation constant (pKa) and lipophilicity index (log P) of tertiary amines were determined; while quaternary ammonium salts were characterized by software-calculated lipophilicity index and surface tension. Biological evaluation aimed at testing acetylcholinesterase and butyrylcholinesterase-inhibiting activity of synthesized compounds. A possible mechanism of action of these compounds was determined by molecular modelling study using combined techniques of docking; molecular dynamics simulations and quantum mechanics calculations
Searching new structural scaffolds for BRAF inhibitors. An integrative study using theoretical and experimental techniques
The identification of the V600E activating mutation in the protein kinase BRAF in around 50% of melanoma patients has driven the development of highly potent small inhibitors (BRAFi) of the mutated protein. To date, Dabrafenib and Vemurafenib, two specific BRAFi, have been clinically approved for the treatment of metastatic melanoma. Unfortunately, after the initial response, tumors become resistant and patients develop a progressive and lethal disease, making imperative the development of new therapeutic options. The main objective of this work was to find new BRAF inhibitors with different structural scaffolds than those of the known inhibitors. Our study was carried out in different stages; in the first step we performed a virtual screening that allowed us to identify potential new inhibitors. In the second step, we synthesized and tested the inhibitory activity of the novel compounds founded. Finally, we conducted a molecular modelling study that allowed us to understand interactions at the molecular level that stabilize the formation of the different molecular complexes. Our theoretical and experimental study allowed the identification of four new structural scaffolds, which could be used as starting structures for the design and development of new inhibitors of BRAF. Our experimental data indicate that the most active compounds reduced significantly ERK½ phosphorylation, a measure of BRAF inhibition, and cell viability. Thus, from our theoretical and experimental results, we propose new substituted hydroxynaphthalenecarboxamides, N-(hetero)aryl-piperazinylhydroxyalkylphenylcarbamates, substituted piperazinylethanols and substituted piperazinylpropandiols as initial structures for the development of new inhibitors for BRAF. Moreover, by performing QTAIM analysis, we are able to describe in detail the molecular interactions that stabilize the different Ligand-Receptor complexes. Such analysis indicates which portion of the different molecules must be changed in order to obtain an increase in the binding affinity of these new ligands.Fil: Campos, Ludmila EstefanĂa. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones BiolĂłgicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias FĂsico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones BiolĂłgicas de San Luis; Argentina. Universidad Nacional de San Luis. Facultad de QuĂmica, BioquĂmica y Farmacia; ArgentinaFil: Garibotto, Francisco MatĂas. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones BiolĂłgicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias FĂsico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones BiolĂłgicas de San Luis; Argentina. Universidad Nacional de San Luis. Facultad de QuĂmica, BioquĂmica y Farmacia; ArgentinaFil: Angelina, Emilio Luis. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de QuĂmica. Laboratorio de Estructura Molecular y Propiedades; ArgentinaFil: Kos, Jiri. Univerzita PalackĂ©ho v Olomouci; RepĂşblica ChecaFil: TomašiÄŤ, Tihomir. Univerza v Ljubljani; EsloveniaFil: Zidar, Nace. Univerza v Ljubljani; EsloveniaFil: Kikelj, Danijel. Univerza v Ljubljani; EsloveniaFil: Gonec, Tomas. VeterinárnĂ a farmaceutická univerzita Brno; RepĂşblica ChecaFil: Marvanova, Pavlina. VeterinárnĂ a farmaceutická univerzita Brno; RepĂşblica ChecaFil: Mokry, Petr. VeterinárnĂ a farmaceutická univerzita Brno; RepĂşblica ChecaFil: Jampilek, Josef. Univerzita PalackĂ©ho v Olomouci; RepĂşblica Checa. Univerzita KomenskĂ©ho v Bratislave; EslovaquiaFil: Alvarez, Sergio Eduardo. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones BiolĂłgicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias FĂsico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones BiolĂłgicas de San Luis; Argentina. Universidad Nacional de San Luis. Facultad de QuĂmica, BioquĂmica y Farmacia; ArgentinaFil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones BiolĂłgicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias FĂsico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones BiolĂłgicas de San Luis; Argentina. Universidad Nacional de San Luis. Facultad de QuĂmica, BioquĂmica y Farmacia; Argentin
An integrative study to identify novel scaffolds for sphingosine kinase 1 inhibitors
Sphingosine kinase 1 (SphK1), the enzyme that produces the bioactive sphingolipid metabolite, sphingosine-1-phosphate, is a promising new molecular target for therapeutic intervention in cancer and inflammatory diseases. In view of its importance, the main objective of this work was to find new and more potent inhibitors for this enzyme possessing different structural scaffolds than those of the known inhibitors. Our theoretical and experimental study has allowed us to identify two new structural scaffolds (three new compounds), which could be used as starting structures for the design and then the development of new inhibitors of SphK1. Our study was carried out in different steps: virtual screening, synthesis, bioassays and molecular modelling. From our results, we propose a new dihydrobenzo[b]pyrimido[5,4-f]azepine and two alkyl{3-/4-[1-hydroxy-2-(4-arylpiperazin-1-yl)ethyl]phenyl}carbamates as initial structures for the development of new inhibitors. In addition, our molecular modelling study using QTAIM calculations, allowed us to describe in detail the molecular interactions that stabilize the different Ligand-Receptor complexes. Such analyses indicate that the cationic head of the different compounds must be refined in order to obtain an increase in the binding affinity of these ligands.Fil: Vettorazzi, Marcela Cristina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones BiolĂłgicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias FĂsico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones BiolĂłgicas de San Luis; ArgentinaFil: Angelina, Emilio Luis. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de QuĂmica. Laboratorio de Estructura Molecular y Propiedades; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Lima, Santiago. Virginia Commonwealth University. School of Medicine; Estados UnidosFil: Gonec, Tomas. Veterinarni A Farmaceuticka Univerzita Brno; RepĂşblica ChecaFil: Otevrel, Jan. Veterinarni A Farmaceuticka Univerzita Brno; RepĂşblica ChecaFil: Marvanova, Pavlina. Veterinarni A Farmaceuticka Univerzita Brno; RepĂşblica ChecaFil: Padrtova, Tereza. Veterinarni A Farmaceuticka Univerzita Brno; RepĂşblica ChecaFil: Mokry, Petr. Veterinarni A Farmaceuticka Univerzita Brno; RepĂşblica ChecaFil: Bobal, Pavel. Veterinarni A Farmaceuticka Univerzita Brno; RepĂşblica ChecaFil: Acosta, Lina M.. Universidad Industrial Santander; ColombiaFil: Palma, Alirio. Universidad Industrial Santander; ColombiaFil: Cobo, Justo. Universidad de JaĂ©n; EspañaFil: Bobalova, Janette. Institute Of Analytical Chemistry Of The Czech Academy Of Sciences; RepĂşblica ChecaFil: Csollei, Jozef. Comenius University; EslovaquiaFil: Malik, Ivan. Comenius University; EslovaquiaFil: Alvarez, Sergio Eduardo. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones BiolĂłgicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias FĂsico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones BiolĂłgicas de San Luis; ArgentinaFil: Spiegel, Sarah. Virginia Commonwealth University. School of Medicine; Estados UnidosFil: Jampilek, Josef. Comenius University; EslovaquiaFil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones BiolĂłgicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias FĂsico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones BiolĂłgicas de San Luis; Argentin
Trends and outcomes for non‑elective neurosurgical procedures in Central Europe during the COVID‑19 pandemic
The world currently faces the novel severe acute respiratory syndrome coronavirus 2 pandemic.
Little is known about the efects of a pandemic on non-elective neurosurgical practices, which have
continued under modifed conditions to reduce the spread of COVID-19. This knowledge might be
critical for the ongoing second coronavirus wave and potential restrictions on health care. We aimed
to determine the incidence and 30-day mortality rate of various non-elective neurosurgical procedures
during the COVID-19 pandemic.A retrospective, multi-centre observational cohort study among
neurosurgical centres within Austria, the Czech Republic, and Switzerland was performed. Incidence of
neurosurgical emergencies and related 30-day mortality rates were determined for a period refecting
the peak pandemic of the frst wave in all participating countries (i.e. March 16th–April 15th, 2020),
and compared to the same period in prior years (2017, 2018, and 2019).A total of 4,752 emergency
neurosurgical cases were reviewed over a 4-year period. In 2020, during the COVID-19 pandemic,
there was a general decline in the incidence of non-elective neurosurgical cases, which was driven by
a reduced number of traumatic brain injuries, spine conditions, and chronic subdural hematomas.
Thirty-day mortality did not signifcantly increase overall or for any of the conditions examined during
the peak of the pandemic.The neurosurgical community in these three European countries observed a
decrease in the incidence of some neurosurgical emergencies with 30-day mortality rates comparable
to previous years (2017–2019). Lower incidence of neurosurgical cases is likely related to restrictions
placed on mobility within countries, but may also involve delayed patient presentation.Medicine, Faculty ofOther UBCNon UBCReviewedFacultyResearcherPostdoctora