Cyclosarin-An Organophosphate Nerve Agent

Organophosphorus compounds ascribed to as nerve agents (sarin, soman, tabun, cyclosarin) are highly toxic, and are considered to be the most dangerous chemical compounds. All apparently share a common mechanism of cholinesterase inhibition and can cause similar sv.m .ot oms. The standard therapy, in the case of organophosphorus poisoning, has the prophylactic use of reversibly acting AChE inhibitors and antidotal administration of AChE reactivators-oximes. Unfortunately, none of these oximes can be regarded as a broad spectrum antidote, ie, effective against all nerve agents. While the presently available oximes (pralidoxime, ohidoxime) are not considered to be sufficiently effective against nerve agents, especially in the case of soman poisoning, the H oximes (HI-6, HLo7) appear to,be very promising antidotes against nerve agents because these are able to protect the experimental animals from toxic effects and improve survival of animals poisoned with supralethal doses. A lot of research has been pursued on the treatment of sarin, soman, and tabun, but cyclosarin was not considered for such a study for a long time. Recently, attention of researchers has also turned to cyclosarin because of its potential use as a chemical warfare agent. Cyclosarin is highly toxic organophosphorus compound which is resistant to conventional oxime therapy. This paper reviews the latest positionof cyclosarin in standpoint of medical treatment by various reactivators considering the ability of various oximes, HI-6, HS-6, BI-6, and KO33 of their reactivation potency

Research on the continuous casting process of CuCrZr alloys with the addition of scandium dedicated for resistance welding electrodes

The article presents the results of research on the metallurgical synthesis of CuCrZr copper alloys with the addition of scandium as a new material for spot welding electrodes for the resistance spot welding of Zn-coated steel sheets. The tested material was manufactured in a continuous casting process in a horizontal arrangement in the form of rod. The alloys were heat treated to determine their hardness and electrical conductivity properties. Zinc diffusion tests into the material structure were carried out on the produced castings, reflecting the conditions accelerating the wear of electrodes during resistance welding of Zn-coated steel sheets

Leptospira interrogans outer membrane protein-based nanohybrid sensor for the diagnosis of leptospirosis

Leptospirosis is an underestimated tropical disease caused by the pathogenic Leptospira species and responsible for several serious health problems. Here, we aimed to develop an ultrasen-sitive DNA biosensor for the rapid and on-site detection of the Loa22 gene of Leptospira interrogans using a gold nanoparticle–carbon nanofiber composite (AuN/CNF)-based screen-printed electrode. Cyclic voltammetry and electrochemical impedance were performed for electrochemical analysis. The sensitivity of the sensor was 5431.74 µA/cm2 /ng with a LOD (detection limit) of 0.0077 ng/µL using cyclic voltammetry. The developed DNA biosensor was found highly specific to the Loa22 gene of L. interrogans, with a storage stability at 4¿ C for 180 days and a 6% loss of the initial response. This DNA-based sensor only takes 30 min for rapid detection of the pathogen, with a higher specificity and sensitivity. The promising results obtained suggest the application of the developed sensor as a point of care device for the diagnosis of leptospirosis.This research was funded by the Indian Council of Medical Research (ICMR), grant Leptos/27/2013-ECD-1. N.C.-M. acknowledges the Portuguese Foundation for Science and Technology under the Horizon 2020 Program (PTDC/PSI-GER/28076/2017), Supported by Excellence project FIM UHK (K.K.)

Potential usage of edible mushrooms and their residues to retrieve valuable supplies for industrial applications

Currently, the food and agricultural sectors are concerned about environmental problems caused by raw material waste, and they are looking for strategies to reduce the growing amount of waste disposal. Now, approaches are being explored that could increment and provide value-added products from agricultural waste to contribute to the circular economy and environmental protection. Edible mushrooms have been globally appreciated for their medicinal properties and nutritional value, but during the mushroom production process nearly one-fifth of the mushroom gets wasted. Therefore, improper disposal of mushrooms and untreated residues can cause fungal disease. The residues of edible mushrooms, being rich in sterols, vitamin D2, amino acids, and polysaccharides, among others, makes it underutilized waste. Most of the published literature has primarily focused on the isolation of bioactive components of these edible mushrooms; however, utilization of waste or edible mushrooms themselves, for the production of value-added products, has remained an overlooked area. Waste of edible mushrooms also represents a disposal problem, but they are a rich source of important compounds, owing to their nutritional and functional properties. Researchers have started exploiting edible mushroom by-products/waste for value-added goods with applications in diverse fields. Bioactive compounds obtained from edible mushrooms are being used in media production and skincare formulations. Furthermore, diverse applications from edible mushrooms are also being explored, including the synthesis of biosorbent, biochar, edible films/coating, probiotics, nanoparticles and cosmetic products. The primary intent of this review is to summarize the information related to edible mushrooms and their valorization in developing value-added products with industrial applications.This research was funded by the UHK (Faculty of Science, VT2019-2021)

Conifers phytochemicals: A valuable forest with therapeutic potential

Conifers have long been recognized for their therapeutic potential in different disorders. Alkaloids, terpenes and polyphenols are the most abundant naturally occurring phytochemicals in these plants. Here, we provide an overview of the phytochemistry and related commercial products obtained from conifers. The pharmacological actions of different phytochemicals present in conifers against bacterial and fungal infections, cancer, diabetes and cardiovascular diseases are also reviewed. Data obtained from experimental and clinical studies performed to date clearly underline that such compounds exert promising antioxidant effects, being able to inhibit cell damage, cancer growth, inflammation and the onset of neurodegenerative diseases. Therefore, an attempt has been made with the intent to highlight the importance of conifer-derived extracts for pharmacological purposes, with the support of relevant in vitro and in vivo experimental data. In short, this review comprehends the information published to date related to conifers’ phytochemicals and illustrates their potential role as drugs.This research was funded by University of Hradec Kralove (Faculty of Science VT 2019-2021)

Design, synthesis and in vitro evaluation of benzothiazole-based ureas as potential ABAD/17β-HSD10 modulators for Alzheimer’s disease treatment

This work was supported by the Ministry of Health of the Czech Republic (no. NV15-28967A), Charles University in Prague (no. GAUK B-CH/992214, SVV 260 291) and the Alzheimer’s Society (specifically The Barcopel Foundation). This research is part-funded by the MSD Scottish Life Sciences fund.Amyloid-beta peptide (Aβ) has been recognized to interact with numerous proteins, which may lead to pathological changes in cell metabolism of Alzheimer’s disease (AD) patients. One such known metabolic enzyme is mitochondrial amyloid-binding alcohol dehydrogenase (ABAD), also known as 17β-hydroxysteroid dehydrogenase type 10 (17β-HSD10). Altered enzyme function caused by the Aβ-ABAD interaction, was previously shown to cause mitochondrial distress and a consequent cytotoxic effect, therefore providing a feasible target in AD drug development. Based on previous frentizole derivatives studies, we report two novel series of benzothiazolyl ureas along with novel insights into the structure and activity relationships for inhibition of ABAD. Two compounds ( 37 , 39 ) were identified as potent ABAD inhibitors, where compound 39 exhibited comparable cytotoxicity with the frentizole standard; however, one-fold higher cytotoxicity than the parent riluzole standard. The calculated and experimental physical chemical properties of the most potent compounds showed promising features for blood-brain barrier penetration.PostprintPeer reviewe

6-benzothiazolyl ureas, thioureas and guanidines are potent inhibitors of ABAD/17β-HSD10 and potential drugs for Alzheimer's disease treatment : design, synthesis and in vitro evaluation

Background : The mitochondrial enzyme amyloid beta-binding alcohol dehydrogenase (ABAD) also known as 17β-hydroxysteroid dehydrogenase type 10 (17β-HSD10) has been connected with the pathogenesis of Alzheimer’s disease (AD). ABAD/ 17β-HSD10 is a binding site for the amyloid-beta peptide (Aβ) inside the mitochondrial matrix where it exacerbates Aβ toxicity. Interaction between these two proteins triggers a series of events leading to mitochondrial dysfunction as seen in AD. Methods : As ABAD’s enzymatic activity is required for mediating Aβ toxicity, its inhibition presents a promising strategy for AD treatment. In this study, a series of new benzothiazolylurea analogues have been prepared and evaluated in vitro for their potency to inhibit ABAD/ 17β-HSD10 enzymatic activity. The most potent compounds have also been tested for their cytotoxic properties and their ability to permeate through blood-brain barrier has been predicted. To explain the structure-activity relationship QSAR and pharmacophore studies have been performed. Results and Conclusions : Compound 12 was identified being the most promising hit compound with good inhibitory activity (IC50 = 3.06 ± 0.40µM) and acceptable cytotoxicity profile comparable to the parent compound of frentizole. The satisfactory physical-chemical properties suggesting its capability to permeate through BBB make compound 12 a novel lead structure for further development and biological assessment.PostprintPeer reviewe