Medicinal Chemistry of Boron-Bearing Compounds for BNCT- Glioma Treatment: Current Challenges and Perspectives

Since its first description, boron neutron capture therapy (BNCT) was a special type of radiotherapy for treatment of cancer and with focus mainly on glioma therapeutic. This procedure requires the selective accumulation of boron into the tumoral cells, and due to this requirement, different boron-enriched compounds have been designed and developed. Efforts to circumvent the selectivity-uptake challenge and other problems, such as solubility, stability, and toxicity, have been to driving force behind the medicinal chemistry field in boron-based compounds. In this regard, a wide diversity of medicinal chemistry hypothesis has been used to obtain new and efficient potential BNCT-glioma drugs. In this chapter, these ideas are analyzed focusing on their medicinal chemistry characteristics

Slowed Development of Natural Products for Chagas Disease, how to Move Forward?

Chagas disease, caused by Trypanosoma cruzi, is considered an endemic disease that affects millions of people causing generating health, economic and social problems. This study provides a review on research and development of new therapies for Chagas based in natural products of plant origin. We observed that there are more than 400 plant species that have been evaluated against different models of Chagas disease, and in some cases, there are interesting results. Challenge that hinders research work is the purification of the active compound and standardization of the chemical profile of whole extracts. The principal common factor that delays clinical testing is the lack of investment for the development of these products at the clinical phase. In the search of a natural, low cost and available drug for Chagas disease, we propose the use of new methodologies to overcome the existing challenges. The use of plant metabolomic technique is proposed as an option with high potential for the identification of biomarkers that could allow the standardization of chemical profiles. Furthermore, we describe the importance of applying good agricultural and manufacturing practices for reaching a successful development of quality phytotherapeutic products

Study for pediatric protocol optimization in chest CT scan

Radiological exams are increasingly used in clinic for diagnostic analysis of different types of pathologies. These exams are associated with a dose that is received by the patient. In addition, the risks in exposure to ionizing radiation are different according to the group which the individual belongs. According to age, the group of children is more radiosensitive than adults. In this work we have obtained values of the air-weighted kerma index for chest scans studies in a General Electric Computed Tomography (CT) scanner model Discovery with 64-channels. Using an adult protocol, two scans have been performed, one using a cylinder standard PMMA phantom while the second one has used an oblong chest phantom designed for a two year old pediatric patient. Furthermore, other protocols have been selected with a constant voltage but changing the X-ray tube current and maintaining the image quality in order to obtain a reduction in the received dose by the pediatric patient. The use of the adult protocol in the child phantom has an air-weighted kerma index of 89.5% greater than the kerma index using the adult phantom. Due small patients receive higher doses; the use of specific protocols for children is important for the dose reduction in CT tests. An optimized pediatric chest protocol is presented, obtaining as a result dose reduction compared with the adult protocol of 62.2%. Because of different CT scanners characteristics and in order to optimize protocols regard to dose and diagnostic image quality, it is necessary to use pediatric phantoms in health centers

Seroprevalencia de la enfermedad de Chagas en embarazadas del departamento de Cordillera en el período 2010-2016 y el comportamiento de la seroprevalencia después de 21 años de la implementación del Programa de Control Prenatal de Chagas

En Paraguay se estima que 165.000 personas están infectadas por Trypanosoma cruzi, agente etiológico de la enfermedad de Chagas, de las cuales 61.000 son mujeres en edad fértil. En 1995 se implementó el Programa de Control Prenatal de Chagasen el departamento de Cordillera, zona endémica del país. El objetivo de este estudio es analizar el comportamiento de la seropositividad a T. cruzien embarazadas en 21 años de control prenatal (período: 1995-2016), con énfasis en el periodo 2010-2016. Elestudio, descriptivo de corte trasversal retrospectivo, empleó los datos obtenidos de los registros de la III Región Sanitaria y de los cinco laboratorios de diagnóstico. Se emplearon los resultados de la serología de 20 distritos en un total de 23.661 embarazadas que asistieron a su control prenatal. En los registros figuran 1.074 embarazadas seropositivas, distribuidas en los cinco laboratorios de referencia, resultando el 5 % la prevalencia de infección con T. cruzien el período 2010-2016. Con una prevalencia al inicio del período de 16%, se evidenció el principal descenso a 6% en el 2014, situación que se mantuvo en una fase cuasi estacionaria hasta el 2016. Se concluye que el sistema de diagnóstico prenatal de la enfermedad de Chagas asociado a los métodos de prevención implementados por el Ministerio de Salud Pública y Bienestar Social, han resultado efectivos. Esta información es útil para, a través de la identificación de las embarazadas seropositivas y el tratamiento correspondiente, controlar la transmisión congénita

Seroprevalencia de la enfermedad de Chagas en embarazadas del departamento de Cordillera en el período 2010-2016 y el comportamiento de la seroprevalencia después de 21 años de la implementación del Programa de Control Prenatal de Chagas

En Paraguay se estima que 165.000 personas están infectadas por Trypanosoma cruzi, agente etiológico de la enfermedad de Chagas, de las cuales 61.000 son mujeres en edad fértil. En 1995 se implementó el Programa de Control Prenatal de Chagas en el departamento de Cordillera, zona endémica del país. El objetivo de este estudio es analizar el comportamiento de la seropositividad a T. cruzi en embarazadas en 21 años de control prenatal (período: 1995-2016), con énfasis en el periodo 2010-2016. El estudio, descriptivo de corte trasversal retrospectivo, empleó los datos obtenidos de los registros de la III Región Sanitaria y de los cinco laboratorios de diagnóstico. Se emplearon los resultados de la serología de 20 distritos en un total de 23.661 embarazadas que asistieron a su control prenatal. En los registros figuran 1.074 embarazadas seropositivas, distribuidas en los cinco laboratorios de referencia, resultando el 5 % la prevalencia de infección con T. cruzi en el período 2010-2016. Con una prevalencia al inicio del período de 16 %, se evidenció el principal descenso a 6 % en el 2014, situación que se mantuvo en una fase cuasi estacionaria hasta el 2016. Se concluye que el sistema de diagnóstico prenatal de la enfermedad de Chagas asociado a los métodos de prevención implementados por el Ministerio de Salud Pública y Bienestar Social, han resultado efectivos. Esta información es útil para, a través de la identificación de las embarazadas seropositivas y el tratamiento correspondiente, controlar la transmisión congénita

Mass spectrometry of 1,2,5-oxadiazole N-oxide derivatives. Use of deuterated analogues in fragmentation pattern studies

This paper reported on the study of fragmentation pattern in mass spectrometry of 1,2,5-oxadiazole N-oxide derivatives involving deuterium-labeled analogues to identify some critical fragmentations. A neutral CH2O loss from 3-hydroxymethyl-N2-oxide-4-phenyl-1,2,5-oxadiazole was confirmed with the corresponding mono-deuterated analogue. An OH loss, involving the oxygen of N-oxide, via β-H and δ-H rearrangement, was clearly revealed from 3-(4-methylpiperazine-1-ylmethyl)-N2-oxide-4-phenyl-1, 2,5-oxadiazole using the adequate tetra-deuterated analogue. N-oxide isomer and deoxygenated analogues were also used to confirm the participation of the oxide moiety in the fragmentation process.Reportamos neste trabalho o estudo sistemático de fragmentação dos derivados de N-óxidos de 1,2,5-oxadiazóis por espectroscopia de massa, usando análogos marcados com deutério para identificar algumas fragmentações críticas. Foi confirmada a perda neutra de CH2O a partir do N2-óxido de 3- hidroximetil-4-fenil-1,2,5-oxidiazol, usando o análogo mono-deuterado. A perda de OH, a partir do oxigênio do N-óxido, por um rearranjo β-H e δ-H, foi claramente verificada a partir do N2-óxido de 3-(4-metilpiperazina-1-metil)-4-fenil-1,2,5-oxidiazol, usando-se o analogo tetra-deuterado adequado. O isômero N-óxido e análogos desoxigenados foram também usados para confirmar a participação do fragmento óxido no processo de defragmentação.Facultad de Ciencias Exacta

Evaluating 5-nitrofurans as trypanocidal agents

The nitroheterocycle nifurtimox, as part of a nifurtimox-eflornithine combination therapy, represents one of a limited number of treatments targeting Trypanosoma brucei, the causative agent of human African trypanosomiasis. The mode of action of this prodrug involves an initial activation reaction catalysed by a type I nitroreductase (NTR), an enzyme found predominantly in prokaryotes, leading to the formation of a cytotoxic unsaturated open chain nitrile metabolite. Here, we evaluate the trypanocidal activity of a library of other 5-nitrofurans against bloodstream form T. brucei as a preliminary step in the identification of additional nitroaromatic compounds that could potentially partner eflornithine. Biochemical screening against purified enzyme revealed that all 5-nitrofurans were effective substrates for TbNTR with the preferred compounds having apparent kcat/KM values approximately 50-fold greater than nifurtimox. For several compounds, in vitro reduction by this nitroreductase yielded products characterized by mass spectroscopy as either unsaturated or saturated open chain nitriles. When tested against bloodstream form T. brucei, many of the derivatives displayed significant growth inhibitory properties with the most potent compounds generating IC50 values around 200 nM. The anti-parasitic activity of the most potent agents was demonstrated to be NTR dependent as parasites having reduced levels of the enzyme displayed resistance to the compounds while parasites over expressing TbNTR showed hypersensitivity. We conclude that other members of the 5-nitrofurans class of nitroheterocycles have potential to treat human African trypanosomiasis perhaps as an alternative partner prodrug to nifurtimox in the next generation of eflornithine-based combinational therapies

Low-temperature redetermination of benzofurazan 1-oxide

In the six-membered ring of the low-temperature crystal structure of benzofurazan 1-oxide, C6H4N2O2, the two C atoms adjacent to the N atoms are linked by a delocalized aromatic bond [1.402 (2) Å]; each is connected to its neighbour by a longer, more localized, bond [1.420 (2), 1.430 (2) Å]. However, the next two bonds in the ring approximate double bonds [1.357 (2), 1.366 (2) Å]. As such, the six-membered ring is better described as a cyclo­hexa­diene system, in contrast to the description in the room-temperature structure reported by Britton & Olson (1979 ▶) [Acta Cryst. B35, 3076–3078]

Metastatic and non-metastatic melanoma imaging using Sgc8-c aptamer PTK7-recognizer

Existe información complementaria en: https://doi.org/10.1038/s41598-021-98828-6Melanoma is one of the most aggressive and deadly skin cancers, and although histopathological criteria are used for its prognosis, biomarkers are necessary to identify the different evolution stages. The applications of molecular imaging include the in vivo diagnosis of cancer with probes that recognize the tumor-biomarkers specific expression allowing external image acquisitions and evaluation of the biological process in quali-quantitative ways. Aptamers are oligonucleotides that recognize targets with high affinity and specificity presenting advantages that make them interesting molecular imaging probes. Sgc8-c (DNA-aptamer) selectively recognizes PTK7-receptor overexpressed in various types of tumors. Herein, Sgc8-c was evaluated, for the first time, in a metastatic melanoma model as molecular imaging probe for in vivo diagnostic, as well as in a non-metastatic melanoma model. Firstly, two probes, radio- and fluorescent-probe, were in vitro evaluated verifying the high specific PTK7 recognition and its internalization in tumor cells by the endosomal route. Secondly, in vivo proof of concept was performed in animal tumor models. In addition, they have rapid clearance from blood exhibiting excellent target (tumor)/non-target organ ratios. Furthermore, optimal biodistribution was observed 24 h after probes injections accumulating almost exclusively in the tumor tissue. Sgc8-c is a potential tool for their specific use in the early detection of melanoma.ANII: POS_NAC_2017_1_14036