Charting the chemical reaction space around the combination of carbonyls, amines, and isocyanoacetates allows the description of new multicomponent processes leading to a variety of unsaturated ...imidazolone scaffolds. The resulting compounds display the chromophore of the green fluorescent protein and the core of the natural product coelenterazine. Despite the competitive nature of the pathways involved, general protocols provide selective access to the desired chemotypes. Moreover, we describe unprecedented reactivity at the C-2 position of the imidazolone core to directly afford C, S, and N-derivatives featuring natural products (e.g. leucettamines), potent kinase inhibitors, and fluorescent probes with suitable optical and biological profiles.
Diabetes is the most prevalent disease that has involved 177 million people all over the world and, due to this, these patients suffer from depression and anxiety and they should use special methods ...for controlling the same. The aim of this research is the study of the effect of problem solving and decision making skill on the rate of the tendency to depression and anxiety.
This research is a quasi-experimental (case-control) study. Statistically, the population of the present study was all diabetic patients of Qaemshahr who were controlled by physicians in 2011-2012. Thirty files were selected randomly from them and divided into two 15 patients' groups (control and subject group) randomly. The measurement tools were Back depression inventory (21 items) and Zank anxiety questionnaire that were distributed among two groups. Then, the subject group participated in eight sessions of teaching problem solving and decision making courses separately, and the second group (control group) did not receive any instruction.
Finally, both groups had passed post-test and the data obtained from the questionnaires were studied by variance analysis statistical methods.
The results showed that teaching problem solving and decision making skills was very effective in reducing diabetic patients' depression and anxiety and resulted in reducing their depression and anxiety.
Trimethylsilyl chloride is an efficient activating agent for azines in isocyanide‐based reactions, which then proceed through a key insertion of the isocyanide into a N−Si bond. The reaction is ...initiated by N activation of the azine, followed by nucleophilic attack of an isocyanide in a Reissert‐type process. Finally, a second equivalent of the same or a different isocyanide inserts into the N−Si bond leading to the final adduct. The use of distinct nucleophiles leads to a variety of α‐substituted dihydroazines after a selective cascade process. Based on computational studies, a mechanistic hypothesis for the course of these reactions was proposed. The resulting products exhibit significant activity against Trypanosoma brucei and T. cruzi, featuring favorable drug‐like properties and safety profiles.
Insert here! Multicomponent reactions (MCRs) with isoquinolines and other azines that proceed through the insertion of an isocyanide into a N−Si bond are described. This novel activation mode enables a variety of transformations to take place with high selectivity under mild reaction conditions. Some of the products showed in vitro activity against the causative agents of trypanosomiasis. TMS=trimethylsilyl.
Growth factor Neuregulin 1 (NRG1) plays an essential role in development and organization of the cerebral cortex. NRG1 and its receptors, ERBB3 and ERBB4, have been implicated in genetic ...susceptibility for schizophrenia. Disease symptoms include asociality and altered social interaction. To investigate the role of NRG1-ERBB signaling in social behavior, mice heterozygous for an Nrg1 null allele (Nrg1+/-), and mice with conditional ablation of Erbb3 or Erbb4 in the central nervous system, were evaluated for sociability and social novelty preference in a three-chambered choice task. Results showed that deficiencies in NRG1 or ERBB3 significantly enhanced sociability. All of the mutant groups demonstrated a lack of social novelty preference, in contrast to their respective wild-type controls. Effects of NRG1, ERBB3, or ERBB4 deficiency on social behavior could not be attributed to general changes in anxiety-like behavior, activity, or loss of olfactory ability. Nrg1+/- pups did not exhibit changes in isolation-induced ultrasonic vocalizations, a measure of emotional reactivity. Overall, these findings provide evidence that social behavior is mediated by NRG1-ERBB signaling.
Left ventricular assist devices (LVADs) have dramatically improved short-term outcomes among patients with advanced heart failure. While neurohormonal blockade (NHB) is the cornerstone of treatment ...for patients with heart failure with reduced ejection fraction, its effect after LVAD placement has not been established. We reviewed medical records of 307 patients who underwent primary LVAD implantation from January 2006 to September 2015 at two institutions in the United States. Patients were followed for at least 2 years post-LVAD implantation or until explantation, heart transplantation, or death. Cox regression analysis stratifying on center was used to assess associations with mortality. Neurohormonal blockade use was treated as a time-dependent predictor. Stepwise selection indicated treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs) (hazard ratio HR = 0.53 0.30-0.95, p = 0.03), age at the time of implantation (HR = 1.28 1.05-1.56 per decade, p = 0.02), length of stay postimplantation (HR = 1.16 1.11-1.21 per week, p < 0.01) and INTERMACS profile of 1 or 2 (HR = 1.86 1.17-2.97, p < 0.01) were independent predictors of mortality. In this large, retrospective study, treatment with ACEIs or ARBs was an independent factor associated with decreased mortality post-LVAD placement.
Imidazolium salts are privileged compounds in organic chemistry, and have valuable biological properties. Recent studies show that symmetric imidazolium salts with bulky moieties can display ...antiparasitic activity against T. cruzi. After developing a facile methodology for the synthesis of tetrasubstituted imidazolium salts from propargylamines and isocyanides, we screened a small library of these adducts against the causative agents of African and American trypanosomiases. These compounds display nanomolar activity against T. brucei and low (or sub) micromolar activity against T. cruzi, with excellent selectivity indexes and favorable molecular properties, thereby emerging as promising hits for the treatment of Chagas disease and sleeping sickness.
The participation of reactants undergoing a polarity inversion along a multicomponent reaction allows the continuation of the transformation with productive domino processes. Thus, indole aldehydes ...in Groebke–Blackburn–Bienaymé reactions lead to an initial adduct which spontaneously triggers a series of events leading to the discovery of novel reaction pathways together with direct access to a variety of linked, fused, and bridged polyheterocyclic scaffolds. Indole 3‐ and 4‐carbaldehydes with suitable isocyanides and aminoazines afford fused adducts through oxidative Pictet–Spengler processes, whereas indole 2‐carbaldehyde yields linked indolocarbazoles under mild conditions, and a bridged macrocycle at high temperature. These novel structures are potent activators of the human aryl hydrocarbon receptor signaling pathway.
By engaging indole aldehydes in an isocyanide multicomponent reaction, the polarity inversion of the indole moiety along the transformation triggers an extension of the domino process, leading to a variety of unprecedented fused, linked, and bridged scaffolds. The processes can be run in parallel and the adducts display remarkable bioactivity as potent ligands of the aryl hydrocarbon receptor.
Bovine theileriosis is important disease in tropical and subtropical areas with great economic losses in livestock husbandry in Iran. The aim of study was to assess the prevalence of Theileria ...annulata infection in cattle and Hyalomma species of Kermanshah Province, Iran. A number of 138 blood samples were randomly taken from examined cattle. The genomic DNA was extracted and PCR was performed to specifically amplify a 721-bp-long fragment of the 30 Kilo Dalton major merozoite surface antigen (30 KDa msa) of T. annulata. The amplified products were digested with TaqI, Rasl, and AluI restriction enzymes. Overall prevalence was 9.44% (13/138) with lymphadnopathy (1.17%) and pale mucosal membrane (1.9%) in Holstein cattle aged <1 year and more than 5 years-old, respectively. Five species of genus Hyalomma (18.8%, 141/750) including Hyalomma anatolicum anatolicum (30.4%), H. anatolicum excavatum (31.2%), H. marginatum (36.8%), H. asiaticum asiaticum (0.7%), and H. detritum (0.7%) were identified. The tick indices for each Hyalomma species were ranged from 0.01 to 0.36. PCR findings indicated that 3 out of 138 blood samples (2.17%) and 19 out of 141 Hyalomma ticks (4.13%) were infected with T. annulata. Amplified PCR products from blood samples generated similar RFLP patterns, but different RFLP pattern for T. annulata from H. anatolicum anatolicum (9.21%) and H. anatolicum excavatum (4.2%). The RFLP patterns of the amplified fragment of the 30 KDa msa of T. annulata indicated the circulation of four different T. annulata isolates of H. anatolicum anatolicum and H. anatolicum excavatum in the region.
Trimethylsilyl chloride is an efficient activating agent for azines in isocyanide‐based reactions, which then proceed through a key insertion of the isocyanide into a N−Si bond. The reaction is ...initiated by N activation of the azine, followed by nucleophilic attack of an isocyanide in a Reissert‐type process. Finally, a second equivalent of the same or a different isocyanide inserts into the N−Si bond leading to the final adduct. The use of distinct nucleophiles leads to a variety of α‐substituted dihydroazines after a selective cascade process. Based on computational studies, a mechanistic hypothesis for the course of these reactions was proposed. The resulting products exhibit significant activity against Trypanosoma brucei and T. cruzi, featuring favorable drug‐like properties and safety profiles.
Hier einfügen! Mehrkomponentenreaktionen (MCRs) mit Isochinolinen und anderen Azinen, bei denen ein Isocyanid in eine N‐Si‐Bindung insertiert, werden beschrieben. Dieser Aktivierungsmodus ermöglicht die Durchführung unterschiedlicher Reaktionen mit hoher Selektivität und unter milden Reaktionsbedingungen. Einige der Produkte sind in vitro gegen Erreger von Trypanosomiasis aktiv. TMS=Trimethylsilyl.
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