Sulfonated
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OBJECTIVES: Due to Albendazole's relatively low efficacy and bioavailability, Echinococcosis has proven a challenge to manage successfully, with several studies investigating ways to improve the outcome, mainly showing mixed results. We, therefore, aimed to evaluate whether Sulfonated Graphene Oxide (S-GO), as nanocarriers, could improve the mentioned outcome. METHODS: Echinococcus protoscoleces were divided into four groups based on the agent they received, which comprised control, S-GO, Albendazole, and Albendazole-loaded S-GO (S-GO-Albendazole). Then, the Bax and Bcl-2 gene expression levels and the number of surviving protoscoleces in each group were determined. RESULTS: Bax gene expression increased by 121% in the 50 μg/ml concentration of the S-GO-Albendazole, while Bcl-2 gene expression decreased by 64%. Moreover, S-GO-Albendazole was approximately 18% more effective at neutralizing protoscoleces than Albendazole and 14% and 31% more effective at improving the expression of the mentioned genes, respectively (p < 0.05). In addition, the number of surviving protoscoleces after exposure to the mentioned concentration reduced by approximately 99%. CONCLUSIONS: S-GO, despite not having significant lethality on protoscoleces, significantly increased the lethality of Albendazole and, therefore, is a suitable nanocarrier. However, we recommend conducting in vivo and clinical studies to more accurately determine this nanocomplex's potential and side effects.
- Publikační typ
- časopisecké články MeSH
The RNA editing core complex (RECC) catalyzes mitochondrial U-insertion/deletion mRNA editing in trypanosomatid flagellates. Some naphthalene-based sulfonated compounds, such as C35 and MrB, competitively inhibit the auto-adenylylation activity of an essential RECC enzyme, kinetoplastid RNA editing ligase 1 (KREL1), required for the final step in editing. Previous studies revealed the ability of these compounds to interfere with the interaction between the editosome and its RNA substrates, consequently affecting all catalytic activities that comprise RNA editing. This observation implicates a critical function for the affected RNA binding proteins in RNA editing. In this study, using the inhibitory compounds, we analyzed the composition and editing activities of functional editosomes and identified the mitochondrial RNA binding proteins 1 and 2 (MRP1/2) as their preferred targets. While the MRP1/2 heterotetramer complex is known to bind guide RNA and promote annealing to its cognate pre-edited mRNA, its role in RNA editing remained enigmatic. We show that the compounds affect the association between the RECC and MRP1/2 heterotetramer. Furthermore, RECC purified post-treatment with these compounds exhibit compromised in vitro RNA editing activity that, remarkably, recovers upon the addition of recombinant MRP1/2 proteins. This work provides experimental evidence that the MRP1/2 heterotetramer is required for in vitro RNA editing activity and substantiates the hypothesized role of these proteins in presenting the RNA duplex to the catalytic complex in the initial steps of RNA editing.
- MeSH
- editace RNA účinky léků genetika MeSH
- guide RNA, Kinetoplastida účinky léků MeSH
- ligasy antagonisté a inhibitory MeSH
- messenger RNA genetika MeSH
- mitochondriální proteiny genetika MeSH
- mitochondrie účinky léků genetika MeSH
- proteiny vázající RNA genetika MeSH
- protozoální proteiny genetika MeSH
- rekombinantní proteiny genetika MeSH
- RNA mitochondriální genetika MeSH
- RNA protozoální genetika MeSH
- Trypanosoma brucei brucei účinky léků MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
... CONTENTS -- WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR LINEAR ALKYLBENZENE SULFONATES AND RELATED ... ... TO READERS OF THE CRITERIA MONOGRAPHS 3 -- ENVIRONMENTAL HEALTH CRITERIA FOR LINEAR ALKYLBENZENE SULFONATES ... ... 8 -- 1.3.2 a-Olefin sulfonates and alkyl sulfates 9 -- 1.4 Environmental transport, distribution, and ... ... transformation 9 -- 1.4.1 Linear alklylbenzene sulfonates 9 -- 1.4.2 a-Olefin sulfonates 10 -- 1.4.3 ... ... Linear alkylbenzene sulfonates and their salts 22 -- Al SUMMARY 22 -- A2. ...
Environmental health criteria ; 169
328 s. : tab. ; 23 cm
- MeSH
- detergenty škodlivé účinky MeSH
- kyseliny sulfonové analogy a deriváty MeSH
- vystavení vlivu životního prostředí MeSH
- Konspekt
- Lékařské vědy. Lékařství
- NLK Obory
- environmentální vědy
- toxikologie
- environmentální vědy
- NLK Publikační typ
- publikace WHO
Dengue virus (DENV) causes 390 million infections per year. Infections can be asymptomatic or range from mild fever to severe haemorrhagic fever and shock syndrome. Currently, no effective antivirals or safe universal vaccine is available. In the present work we tested different gold nanoparticles (AuNP) coated with ligands ω-terminated with sugars bearing multiple sulfonate groups. We aimed to identify compounds with antiviral properties due to irreversible (virucidal) rather than reversible (virustatic) inhibition. The ligands varied in length, in number of sulfonated groups as well as their spatial orientation induced by the sugar head groups. We identified two candidates, a glucose- and a lactose-based ligand showing a low EC50 (effective concentration that inhibit 50% of the viral activity) for DENV-2 inhibition, moderate toxicity and a virucidal effect in hepatocytes with titre reduction of Median Tissue Culture Infectious Dose log10TCID50 2.5 and 3.1. Molecular docking simulations complemented the experimental findings suggesting a molecular rationale behind the binding between sulfonated head groups and DENV-2 envelope protein.
- MeSH
- antivirové látky chemie farmakologie MeSH
- buněčné linie MeSH
- buňky Hep G2 MeSH
- Cercopithecus aethiops MeSH
- dengue farmakoterapie MeSH
- hepatocyty virologie MeSH
- kovové nanočástice chemie MeSH
- lidé MeSH
- ligandy MeSH
- nádorové buněčné linie MeSH
- simulace molekulového dockingu MeSH
- Vero buňky MeSH
- virus dengue účinky léků MeSH
- zlato chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Sulfony se řadí k několika málo lékům, jejichž potencionální užití v dermatologii nabývá skutečně značný rozsah a které jsou v řadě případů podceňovány. Tento článek se zabývá chemickou strukturou, farmakologií, mechanismy působení včetně protizánětlivého a antiprotozoálního účinku, užitím ve schválených indikacích, vedlejšími účinky, užitím v neschválených indikacích v dermatologii. Uvedené znalosti mohou napomoci v rozhodovacím procesu o nasazení těchto typů léků.
Sulfones are regarded as drugs with ever increasing therapeutical potential in different entities in dermatology. Possible indications cover a range of skin disorders and they are frequently underestimated. This article deals with aspects of chemical structure, pharmacology, mechanism of action including anti-inflammatory and antiprotozoal activities, approved indications, side effects, and summarizes unapproved indications – both recommended and not recommended in dermatology. Data included could be helpful in our decision to use such drug in the treatment of various diseases.
- MeSH
- acne vulgaris farmakoterapie MeSH
- antiinfekční látky MeSH
- bulózní pemfigoid diagnóza farmakoterapie MeSH
- chemotaxe fyziologie MeSH
- dapson * aplikace a dávkování farmakologie škodlivé účinky terapeutické užití MeSH
- dermatitis herpetiformis diagnóza terapie MeSH
- epidermolysis bullosa acquisita farmakoterapie MeSH
- Kaposiho sarkom diagnóza farmakoterapie MeSH
- kožní nemoci * diagnóza farmakoterapie MeSH
- lidé MeSH
- lineární IgA bulózní dermatóza farmakoterapie MeSH
- lymfocyty fyziologie MeSH
- peroxidasa fyziologie MeSH
- receptory interleukinu-8A fyziologie MeSH
- sulfony farmakologie terapeutické užití MeSH
- systémový lupus erythematodes farmakoterapie MeSH
- Check Tag
- lidé MeSH
Schistosomiasis, a parasitic disease caused by blood flukes of the genus Schistosoma, is a global health problem with over 200 million people infected. Treatment relies on just one drug, and new chemotherapies are needed. Schistosoma mansoni cathepsin B1 (SmCB1) is a critical peptidase for the digestion of host blood proteins and a validated drug target. We screened a library of peptidomimetic vinyl sulfones against SmCB1 and identified the most potent SmCB1 inhibitors reported to date that are active in the subnanomolar range with second order rate constants (k2nd) of ∼2 × 105 M-1 s-1. High resolution crystal structures of the two best inhibitors in complex with SmCB1 were determined. Quantum chemical calculations of their respective binding modes identified critical hot spot interactions in the S1' and S2 subsites. The most potent inhibitor targets the S1' subsite with an N-hydroxysulfonic amide moiety and displays favorable functional properties, including bioactivity against the pathogen, selectivity for SmCB1 over human cathepsin B, and reasonable metabolic stability. Our results provide structural insights for the rational design of next-generation SmCB1 inhibitors as potential drugs to treat schistosomiasis.
