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1.
《Comptes Rendus Chimie》2015,18(8):823-833
The redox response of three anthracenediones; 4,8-dihydroxy-9,10-dioxo-9,10-dihydroanthracen-1-yl acetate (HACAD), 1,4,5-trihydroxyanthracene-9,10-dione (HAD) and 1,4,5-trihydroxy-2-methyl-3-(3-oxobutyl)anthracene-9,10-dione (HOAD) was probed at the surface of a glassy carbon electrode (GCE) over a wide pH range from pH 3 to pH 12 using voltammetric techniques. Cyclic voltammetry (CV) allowed us to evaluate the redox processes in general. Temperature-dependent sweep rate experiments allowed us to obtain kinetic parameters like the diffusion coefficient and the electron transfer rate constant, which were further used to evaluate the thermodynamics of the processes. Differential pulse voltammetry (DPV) allowed the determination of the number of electrons and protons involved in the Faradaic processes. In addition, square-wave voltammetry (SWV) allowed us to assess the reversible/irreversible nature of the electrode processes and allowed the determination of analytical parameters, such as the limit of detection and the limit of quantification. A thorough UV–vis spectroscopy, in a wide pH range, allowed the determination of the acid-base dissociation constant, pKa, and of the molar extinction coefficient. The pKa values determined by different methods were found to be in very good agreement. 相似文献
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Konstantin V. Kudryavtsev Dmitry A. Shulga Vladimir I. Chupakhin Elena I. Sinauridze Fazly I. Ataullakhanov Sergey Z. Vatsadze 《Tetrahedron》2014
A library of saturated bridged heterocycles based on 3,6-diazabicyclo[3.2.1]octane-2,4-dione and bispidine scaffolds (mean compound molecular weight is approximately 300 Da) with up to three stereocenters and four diversity points has been synthesized. Synthetic scaffold modifications leading to an increase in molecular complexity were studied. Well-defined stereochemical structures of both compound sets was confirmed by X-ray studies and halogenoaryl substituents were inserted appropriately for the design of novel non-basic serine protease inhibitors. Comprehensive molecular modeling has been performed for all synthesized compounds giving rationales of ligand–enzyme interactions with thrombin and trypsin. Biological testing confirmed moderate inhibitory activity of halogen-substituted saturated diazabicyclic small molecules towards thrombin. 相似文献
3.
An electrochemical biosensor capable of indirect detection of DNA damage induced by any one of the three endocrine-disrupting compounds (EDCs) – bisphenol A (BPA), 4-nonylphenol (NP) and 4-t-octylphenol (OP), has been researched and developed. The methylene blue (MB) dye was used as the redox indicator. The glassy carbon electrode (GCE) was modified by the assembled dsDNA/graphene oxide-chitosan/gold nano-particles to produce a dsDNA/GO-CS/AuNPs/GCE sensor. It was characterized with the use of electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and scanning electron microscopy (SEM) techniques. The loading/release of the MB dye by the dsDNA/GO-CS/AuNPs film was investigated, and the results showed that the process was reversible. Based on this, the sensor was used to measure the difference between the loading capabilities of intact and damaged dsDNA in the films. The sensor was then successfully applied to detect DNA damage electrochemically. The differential pulse voltammetry (DPV) peak current ratio for MB, observed before and after DNA damage, increased linearly in the presence the BPA, NP or OP compounds; the treatment range was 10–60 min, and the respective damage rates were 0.0069, 0.0044 and 0.0031 min−1, respectively. These results were confirmed by the binding constants: 2.09 × 106 M−1 (BPA-DNA), 1.28 × 106 M−1 (NP-DNA) and 9.33 × 105 M−1 (OP-DNA), all of which were obtained with the use of differential pulse stripping voltammetry (DPSV). 相似文献
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This paper demonstrates the effectiveness of using the redox couple to investigate DNA monolayers, and compares the potential advantages of this system to the standard redox couple. B-DNA monolayers were converted to M-DNA by incubation in buffer containing 0.4 mM Zn2+ at pH 8.6 and studied by cyclic voltammetry (CV), impedance spectroscopy (IS) and chronoamperometry (CA) with . Compared to B-DNA, M-DNA showed significant changes in CV, IS and CA spectra. However, only small changes were observed when the monolayers were incubated in Mg2+ at pH 8.6 or in Zn2+ at pH 6.0. The heterorgeneous electron-transfer rate (kET) between the redox probe and the surface of a bare gold electrode was determined to be 5.7 × 10−3 cm/s. For a B-DNA modified electrode, the kET through the monolayer was too slow to be measured. However, under M-DNA conditions, a kET of 1.5 × 10−3 cm/s was reached. As well, the percent change in resistance to charge transfer, measured by IS, was used to illustrate the dependence of M-DNA formation on pH. This result is consistent with Zn2+ ions replacing the imino protons on thymine and guanine residues. The redox couple was also effective in differentiating between single-stranded and double-stranded DNA during de-hybridization and rehybridization experiments. 相似文献
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Isabel V. L. Wilkinson Kelly J. Perkins Hannah Dugdale Lee Moir Aini Vuorinen Maria Chatzopoulou Sarah E. Squire Sebastian Monecke Alexander Lomow Marcus Geese Philip D. Charles Peter Burch Jonathan M. Tinsley Graham M. Wynne Stephen G. Davies Francis X. Wilson Fraydoon Rastinejad Shabaz Mohammed Kay E. Davies Angela J. Russell 《Angewandte Chemie (International ed. in English)》2020,59(6):2420-2428
Duchenne muscular dystrophy (DMD) is a fatal muscle‐wasting disease arising from mutations in the dystrophin gene. Upregulation of utrophin to compensate for the missing dystrophin offers a potential therapy independent of patient genotype. The first‐in‐class utrophin modulator ezutromid/SMT C1100 was developed from a phenotypic screen through to a Phase 2 clinical trial. Promising efficacy and evidence of target engagement was observed in DMD patients after 24 weeks of treatment, however trial endpoints were not met after 48 weeks. The objective of this study was to understand the mechanism of action of ezutromid which could explain the lack of sustained efficacy and help development of new generations of utrophin modulators. Using chemical proteomics and phenotypic profiling we show that the aryl hydrocarbon receptor (AhR) is a target of ezutromid. Several lines of evidence demonstrate that ezutromid binds AhR with an apparent KD of 50 nm and behaves as an AhR antagonist. Furthermore, other reported AhR antagonists also upregulate utrophin, showing that this pathway, which is currently being explored in other clinical applications including oncology and rheumatoid arthritis, could also be exploited in future DMD therapies. 相似文献
8.
Development of nitroxide‐based theranostic compounds that act both as anti‐inflammatory drugs and brain redox imaging probes in MRI
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Miho C. Emoto Shingo Sato Hirotada G. Fujii 《Magnetic resonance in chemistry : MRC》2016,54(9):705-711
Theranostic probes provide both therapeutic and diagnostic imaging capabilities in one molecule and show significant promise for use in magnetic resonance imaging (MRI) examinations. The present study describes for the first time the synthesis and utility of nitroxide‐based contrast agents exhibiting a nonsteroidal anti‐inflammatory drug effect. The target theranostic probes were prepared by connecting the carboxyl group of ibuprofen or ketoprofen to the hydroxyl group of 3‐hydroxymethyl‐2,2,5,5‐tetramethylprrolidine‐1‐oxyl by a condensation reaction in the presence of dicyclohexylcarbodiimide and 4‐dimethylaminopyridine in dichloromethane. MRI of mouse heads after administration of either synthesized theranostic probe indicated that the probes enter the brain by passing through the blood–brain barrier (BBB), resulting in T1 contrast enhancement in mouse brain. This enhancement persisted for the duration of the half‐life of about 40 min, which is longer than that obtained by most of pyrrolidine nitroxide molecules. The therapeutic capacities of these theranostic probes were examined using a lipopolysaccharide (LPS)‐induced brain inflammation model. The production of nitric oxide, an inflammation marker in septic mouse brain induced by LPS, was remarkably inhibited by the addition of either synthesized probe, indicating that they also act as anti‐inflammatory drugs. The present results indicate that nitroxide‐based theranostic probes act as both BBB‐permeable redox‐sensitive contrast agents and as an anti‐inflammatory drug in septic mouse brain. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献
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In this work, different nitroaromatic compounds were successfully reduced to their corresponding aromatic amines with excellent conversion and selectivity in methanol at 50 °C by using Pd‐Pt nanoparticles immobilized on the modified grapheme oxide (m‐GO) and hydrogen as the reducing source. The catalytic efficiency of Pd and Pd‐Pt loading on the modified GO was investigated for the reduction of various nitroaromatic compounds, and the Pd‐Pt/m‐GO system demonstrated the highest conversion and selectivity. The catalyst was characterized by different techniques including FT‐IR, Raman, UV–Vis, XRD, BET, XPS, FESEM, EDS, and TEM. The metal nanoparticles with the size of less than 10 nm were uniformly distributed on the m‐GO. The catalyst could be reused at least five times without losing activity, showing the stability of the catalyst structure. Finally, the efficiency of the prepared catalyst was compared with Pd‐Pt/AC, and Pd‐Pt/GO catalysts. 相似文献
11.
《Journal of Saudi Chemical Society》2022,26(3):101473
There is currently a global COVID-19 pandemic caused by the severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) and its variants. This highly contagious viral disease continues to pose a major health threat global. The discovery of vaccinations is not enough to prevent their spread and dire consequences. To take advantage of the current drugs and isolated compounds, and immediately qualifying approach is required. The aim of our research is evaluation the potency for natural antiviral compounds against the SARS CoV-2 Mpro. Molecular docking of four phenolic compounds from Phillyrea angustifolia leaves with SARS-CoV-2 Mpro has been conducted. Similarly, the stability of selected ligand–protein interactions has been determined using MD simulations. Moreover, the quantitative structure–activity relationship (QSAR), MMGBSA binding energies, pharmacokinetics, and drug-likeness predictions for selected phenolic have been reported. The selected phenolic compounds (Luteolin-7-O-glucoside, Apigenin-7-O-glucoside, Demethyl-oleuropein, and Oleuropein aglycone) revealed strong binding contacts in the two active pockets of a target protein of SARS-CoV-2 Mpro with the docking scores and highest binding energies with a binding energy of ?8.2 kcal/mol; ?7.8 kcal/mol; ?7.2 kcal/mol and ?7.0 kcal/mol respectively. Both Demethyloleoeuropein and Oleuropein aglycone can interact with residues His41 and Cys145 (catalytic dyad) and other amino acids of the binding pocket of Mpro. According to QSAR, studies on pharmacokinetics and drug-like properties suggested that oleuropein aglycone could be the best inhibitor of SARS-CoV-2 for new drug design and development. Further in vivo, in vitro, and clinical studies are highly needed to examine the potential of these phenolic compounds in the fight against COVID-19. 相似文献
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Bicyclic sulfonamides were synthesized from 4-alkenyl N-alkenylsulfonyl l-prolines using a ring-closure metathesis reaction. Three types of bicyclic sulfonamides varying in the size of the second ring (5,5; 5,6; 5,7) were synthesized. A sulfonamide counterpart of an indolizidinone 2-carboxylic acid was synthesized and evaluated for its activity against the enzyme thrombin. 相似文献
14.
Mala Nath 《应用有机金属化学》2008,22(10):598-612
A comprehensive review on toxicity of organotin compounds including sources of their intake and mode of action, and cardiovascular activity of organotin compounds is presented. Further research to develop novel useful organotin compounds having hypertensive activity needs to be carried out. Copyright © 2008 John Wiley & Sons, Ltd. 相似文献
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The redox potentials of the cobalticenium–cobaltocene couple have been determined voltammetrically in several aqueous–organic mixed solvents. The cosolvents studied were dimethylformamide, acetone, 1,4-dioxane (all three disrupting the 3D network of the water’s hydrogen bonds), propylenecarbonate (at low content structure-making, at higher – structure-breaking), and glycerol that incorporates into the 3D network. Cobalticenium spectra demonstrate the absence of ion pairs and solute–cosolvent complexes. The liquid junction potentials water-mixed solvent in the range of the cosolvent concentrations studied are small. At equal volume fractions of structure-breaking cosolvents the shifts of redox potential relative to water are similar. The potential shifts are more than by order of magnitude higher than those corresponding to the change of the mixed solvent’s dielectric constant. This is explained as due to disruption of the water hydrogen bonded structure, and disappearance therefore of the water anomalous dielectric response. The cobalticenium redox potential in the hypothetic “structureless” water was estimated as being ∼70 mV more positive than in real water. This is the potential that should be compared directly with the data for practically unstructured aprotic solvents. 相似文献
16.
V. A. Sadykov A. Ya. Rozovskii V. V. Lunin G. I. Lin G. M. Alikina G. A. Buchtiyarova B. P. Zolotovskii S. A. Beloshapkin 《Reaction Kinetics and Catalysis Letters》1999,66(2):337-341
The rate-limiting stage of heterogeneous catalytic redox reactions with participation of strongly bound surface species, such
as nitrates, carbonates and sulfites, is the interaction of these heteroatomic oxidants with the reducing agents. It appears
to be mainly determined by their bonding strength with the surface, being independent of the nature of the central atom (carbon,
sulfur, nitrogen) and the energy of its bond with oxygen. 相似文献
17.
Dr. Suxing Jin Dr. Nafees Muhammad Yuewen Sun Yehong Tan Hao Yuan Dongfan Song Prof. Dr. Zijian Guo Prof. Dr. Xiaoyong Wang 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(51):23513-23521
Breast cancer (BC) is one of the most common malignancies in women and often accompanied by inflammatory processes. Cyclooxygenase-2 (COX-2) plays a vital role in the progression of BC, correlating with the expression of programmed death-ligand 1 (PD-L1). Overexpression of PD-L1 contributes to the immune escape of cancer cells, and its blockade would stimulate anticancer immunity. Two multispecific platinum(IV) complexes DNP and NP were prepared using non-steroidal antiinflammatory drug naproxen (NPX) as axial ligand(s) to inhibit the BC cells. DNP exhibited high cytotoxicity and antiinflammatory properties superior over NP, cisplatin and NPX; moreover, it displayed potent antitumor activity and almost no general toxicity in mice bearing triple-negative breast cancer (TNBC). Mechanistic studies revealed that DNP could downregulate the expression of COX-2 and PD-L1 in vitro and vivo, inhibit the secretion of prostaglandin, reduce the expression of BC-associated protein BRD4 and phosphorylation of extracellular signal-regulated kinases 1/2 (Erk1/2), and block the oncogene c-Myc in BC cells. These findings demonstrate that DNP is capable of intervening in inflammatory, immune, and metastatic processes of BC, thus presenting a new mechanism of action for anticancer platinum(IV) complexes. The multispecificity offers a special superiority for DNP to treat TNBC by combining chemotherapy and immunotherapy in one molecule. 相似文献
18.
Swarnagowri Nayak Santosh L. Gaonkar Ebraheem Abdu Musad Abdullah Mohammed AL Dawsar 《Journal of Saudi Chemical Society》2021,25(8):101284
Chemotherapy is an important therapeutic approach for the treatment of cancer. Currently, many anticancer drugs are available in the market that plays an important role in cancer treatment, but concerns such as, drug resistance and side effects create an urgent need for the development of new anti-tumor drugs with high potency and less side effects. Heterocycles are of great interest due to their fascinating anticancer activity. Among them, 1,3,4-oxadiazoles showed attracting anti-tumor activity and its derivatives are under clinical trials for the treatment of cancer. Hybridization of 1,3,4-oxadiazole moiety with other heterocyclic pharmacophoresis a promising approach to overcome various disadvantages of current anticancer drugs such as drug resistance, toxicity, and other side effects. Thus, 1,3,4-oxadiazole-heterocycle hybrids occupy a significant position in the discovery of anti-tumor drugs. Among the reported oxadiazole-based hybrids reviewed here, compounds 45i, 59j, and 62x showed the highest anticancer activity with IC50 values in the nanomolar range. This review summarizes the recent developments in the anticancer potential, structure–activity relationships, and mechanisms of actions of 1,3,4-oxadiazole-heterocycle hybrids. 相似文献
19.
Caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the COVID-19 pandemic is ongoing, with no proven safe and effective vaccine to date. Further, effective therapeutic agents for COVID-19 are limited, and as a result, the identification of potential small molecule antiviral drugs is of particular importance. A critical antiviral target is the SARS-CoV-2 main protease (Mpro), and our aim was to identify lead compounds with potential inhibitory effects. We performed an initial molecular docking screen of 300 small molecules, which included phenolic compounds and fatty acids from our OliveNet™ library (224), and an additional group of curated pharmacological and dietary compounds. The prototypical α-ketoamide 13b inhibitor was used as a control to guide selection of the top 30 compounds with respect to binding affinity to the Mpro active site. Further studies and analyses including blind docking were performed to identify hypericin, cyanidin-3-O-glucoside and SRT2104 as potential leads. Molecular dynamics simulations demonstrated that hypericin (ΔG = -18.6 and -19.3 kcal/mol), cyanidin-3-O-glucoside (ΔG = -50.8 and -42.1 kcal/mol), and SRT2104 (ΔG = -8.7 and -20.6 kcal/mol), formed stable interactions with the Mpro active site. An enzyme-linked immunosorbent assay indicated that, albeit, not as potent as the covalent positive control (GC376), our leads inhibited the Mpro with activity in the micromolar range, and an order of effectiveness of hypericin and cyanidin-3-O-glucoside > SRT2104 > SRT1720. Overall, our findings, and those highlighted by others indicate that hypericin and cyanidin-3-O-glucoside are suitable candidates for progress to in vitro and in vivo antiviral studies. 相似文献
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In the face of the recent pandemic and emergence of infectious diseases of viral origin, research on parasitic diseases such as malaria continues to remain critical and innovative methods are required to target the rising widespread resistance that renders conventional therapies unusable. The prolific use of auxiliary metallo-fragments has augmented the search for novel drug regimens in an attempt to combat rising resistance. The development of organometallic compounds (those containing metal-carbon bonds) as antimalarial drugs has been exemplified by the clinical development of ferroquine in the nascent field of Bioorganometallic Chemistry. With their inherent physicochemical properties, organometallic complexes can modulate the discipline of chemical biology by proffering different modes of action and targeting various enzymes. With the beneficiation of platinum group metals (PGMs) in mind, this review aims to describe recent studies on the antimalarial activity of PGM-based organometallic complexes. This review does not provide an exhaustive coverage of the literature but focusses on recent advances of bioorganometallic antimalarial drug leads, including a brief mention of recent trends comprising interactions with biomolecules such as heme and intracellular catalysis. This resource can be used in parallel with complementary reviews on metal-based complexes tested against malaria. 相似文献