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Garnering inspiration from biological compound eyes, artificial vision systems boasting a vivid range of diverse visual functional traits have come to the fore recently. However, most of these artificial systems rely on transformable electronics, which suffer from the complexity and constrained geometry of global deformation, as well as potential mismatches between optical and detector units. Here, we present a unique pinhole compound eye that combines a three-dimensionally printed honeycomb optical structure with a hemispherical, all-solid-state, high-density perovskite nanowire photodetector array. The lens-free pinhole structure can be designed and fabricated with an arbitrary layout to match the underlying image sensor. Optical simulations and imaging results matched well with each other and substantiated the key characteristics and capabilities of our system, which include an ultrawide field of view, accurate target positioning, and motion tracking function. We further demonstrate the potential of our unique compound eye for advanced robotic vision by successfully completing a moving target tracking mission.
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Carbon monoxide (CO) is an endogenously produced gaseous signaling molecule with demonstrated pharmacological effects. In studying CO biology, three delivery forms have been used: CO gas, CO in solution, and CO donors of various types. Among the CO donors, four carbonyl complexes with either a transition metal ion or borane (BH3) (termed CO-releasing molecules or CORMs) have played the most prominent roles appearing in over 650 publications. These are CORM-2, CORM-3, CORM-A1, and CORM-401. Intriguingly, there have been unique biology findings that were only observed with these CORMs, but not CO gas; yet these properties were often attributed to CO, raising puzzling questions as to why CO source would make such a fundamental difference in terms of CO biology. Recent years have seen a large number of reports of chemical reactivity (e.g., catalase-like activity, reaction with thiol, and reduction of NAD(P)+) and demonstrated CO-independent biological activity for these four CORMs. Further, CORM-A1 releases CO in an idiosyncratic fashion; CO release from CORM-401 is strongly influenced or even dependent on reaction with an oxidant and/or a nucleophile; CORM-2 mostly releases CO2, not CO, after a water-gas shift reaction except in the presence of a strong nucleophile; and CORM-3 does not release CO except in the presence of a strong nucleophile. All these beg the question as to what constitutes an appropriate CO donor for studying CO biology. This review critically summarizes literature findings related to these aspects, with the aim of helping result interpretation when using these CORMs and development of essential criteria for an appropriate donor for studying CO biology.
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Boranos , Compostos Organometálicos , Compostos Organometálicos/farmacologia , Boranos/química , Boranos/farmacologia , Biologia , Monóxido de Carbono/farmacologiaRESUMO
Reactive sulfur species (RSS), such as H2S, hydrogen polysulfide (H2Sn, n ≥ 2), and hydropersulfides (RSSnH, n ≥ 1), are known to mediate diverse signaling pathways and possess a plethora of exciting therapeutic opportunities. Historically, due to the rapid inter-conversion among those species in vivo, the biological differences of distinct sulfur species were often overlooked. These species were considered to enrich the global sulfur pool in almost an equal fashion. However, advancement in this field has revealed that sulfur species at different oxidation states result in different pharmacological effects including scavenging reactive oxygen species (ROS), activating ion channels, and exhibiting analgesic effects. Here, we summarize recent advances in studying the biological and pharmacological differences of distinct sulfur species; discuss this phenomenon from the view of chemical properties and sulfur signaling pathways; and lay out a roadmap to transforming such new knowledge into general principles in developing sulfur-based therapeutics.
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Sulfeto de Hidrogênio , Pró-Fármacos , Sulfeto de Hidrogênio/metabolismo , Pró-Fármacos/farmacologia , Sulfetos/farmacologia , Sulfetos/metabolismo , Enxofre/metabolismoRESUMO
Spherical geometry, adaptive optics, and highly dense network of neurons bridging the eye with the visual cortex, are the primary features of human eyes which enable wide field-of-view (FoV), low aberration, excellent adaptivity, and preprocessing of perceived visual information. Therefore, fabricating spherical artificial eyes has garnered enormous scientific interest. However, fusing color vision, in-device preprocessing and optical adaptivity into spherical artificial eyes has always been a tremendous challenge. Herein, we demonstrate a bionic eye comprising tunable liquid crystal optics, and a hemispherical neuromorphic retina with filter-free color vision, enabled by wavelength dependent bidirectional synaptic photo-response in a metal-oxide nanotube/perovskite nanowire hybrid structure. Moreover, by tuning the color selectivity with bias, the device can reconstruct full color images. This work demonstrates a unique approach to address the color vision and optical adaptivity issues associated with artificial eyes that can bring them to a new level approaching their biological counterparts.
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Visão de Cores , Nanofios , Próteses Visuais , Humanos , Retina/fisiologia , ÓxidosRESUMO
Carbon monoxide (CO) is an endogenous signaling molecule with demonstrated ability to modulate immune responses and to engage key components of the circadian clock. Further, CO has been pharmacologically validated for its therapeutic benefits in animal models of various pathological conditions. For the development of CO-based therapeutics, new delivery forms are needed to address the inherent limitations of using inhaled CO for therapeutic applications. Along this line, there have been metal- and borane-carbonyl complexes reported as CO-release molecules (CORMs) for various studies. CORM-A1 is among the four most widely used CORMs in examining CO biology. Such studies are predicated on the assumptions that CORM-A1 (1) releases CO efficiently and reproducibly under commonly used experimental conditions and (2) does not have meaningful CO-independent activities. In this study, we demonstrate the important redox properties of CORM-A1 leading to the reduction of bio-relevant molecules such as NAD+ and NADP+ under near-physiological conditions; such reduction reciprocally facilitates CO release from CORM-A1. We further demonstrate that CO-release yield and rate from CORM-A1 are highly dependent on various factors such as the medium used, buffer concentrations, and redox environment; these factors seem to be so idiosyncratic that we were unable to find a uniform mechanistic explanation. Under standard experimental conditions, CO release yields were found to be low and highly variable (0.5-15%) in the initial 15 min unless in the presence of certain reagents, e.g. NAD+ or high concentrations of buffer. The significant chemical reactivity of CORM-A1 and the highly variable nature of CO release under near-physiological conditions suggest the need for much more consideration of appropriate controls, if available, and caution in using CORM-A1 as a CO surrogate in biological studies.
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Extensive studies in the last few decades have led to the establishment of CO as an endogenous signaling molecule and subsequently to the exploration of CO's therapeutic roles. In the current state, there is a critical conundrum in CO-related research: the extensive knowledge of CO's biological effects and yet an insufficient understanding of the quantitative correlations between the CO concentration and biological responses of various natures. This conundrum is partially due to the difficulty in examining precise concentration-response relationships of a gaseous molecule. Another reason is the need for appropriate tools for the sensitive detection and concentration determination of CO in the biological system. We herein report a new chemical approach to the design of fluorescent CO probes through de novo construction of fluorophores by a CO insertion-initiated lactamization reaction, which allows for ultra-low background and exclusivity in CO detection. Two series of CO detection probes have been designed and synthesized using this strategy. Using these probes, we have extensively demonstrated their utility in quantifying CO in blood, tissue, and cell culture and in cellular imaging of CO from exogenous and endogenous sources. The probes described will enable many biology and chemistry labs to study CO's functions in a concentration-dependent fashion with very high sensitivity and selectivity. The chemical and design principles described will also be applicable in designing fluorescent probes for other small molecules.
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Monóxido de Carbono , Corantes Fluorescentes , Corantes Fluorescentes/químicaRESUMO
The rapid and persistent emergence of drug-resistant bacteria poses a looming public health crisis. The possible task of developing new sets of antibiotics to replenish the existing ones is daunting to say the least. Searching for adjuvants that restore or even enhance the potency of existing antibiotics against drug-resistant strains of bacteria represents a practical and cost-effective approach. Herein, we describe the discovery of potent adjuvants that extend the antimicrobial spectrum of existing antibiotics and restore their effectiveness toward drug-resistant strains including mcr-1-expressing strains. From a library of cationic compounds, MD-100, which has a diamidine core structure, was identified as a potent antibiotic adjuvant against Gram-negative bacteria. Further optimization efforts including the synthesis of â¼20 compounds through medicinal chemistry work led to the discovery of a much more potent compound MD-124. MD-124 was shown to sensitize various Gram-negative bacterial species and strains, including multidrug resistant pathogens, toward existing antibiotics with diverse mechanisms of action. We further demonstrated the efficacy of MD-124 in an ex vivo skin infection model and in an in vivo murine systemic infection model using both wild-type and drug-resistant Escherichia coli strains. MD-124 functions through selective permeabilization of the outer membrane of Gram-negative bacteria. Importantly, bacteria exhibited low-resistance frequency toward MD-124. In-depth computational investigations of MD-124 binding to the bacterial outer membrane using equilibrium and steered molecular dynamics simulations revealed key structural features for favorable interactions. The very potent nature of such adjuvants distinguishes them as very useful leads for future drug development in combating bacterial drug resistance.
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Antibacterianos , Proteínas de Escherichia coli , Adjuvantes Farmacêuticos/farmacologia , Animais , Antibacterianos/química , Farmacorresistência Bacteriana , Farmacorresistência Bacteriana Múltipla , Escherichia coli , Bactérias Gram-Negativas , CamundongosRESUMO
Carbon monoxide (CO) has been firmly established as an endogenous signaling molecule with a variety of pathophysiological and pharmacological functions, including immunomodulation, organ protection, and circadian clock regulation, among many others. In terms of its molecular mechanism(s) of action, CO is known to bind to a large number of hemoproteins with at least 25 identified targets, including hemoglobin, myoglobin, neuroglobin, cytochrome c oxidase, cytochrome P450, soluble guanylyl cyclase, myeloperoxidase, and some ion channels with dissociation constant values spanning the range of sub-nM to high µM. Although CO's binding affinity with a large number of targets has been extensively studied and firmly established, there is a pressing need to incorporate such binding information into the analysis of CO's biologic response in the context of affinity and dosage. Especially important is to understand the reservoir role of hemoglobin in CO storage, transport, distribution, and transfer. We critically review the literature and inject a sense of quantitative assessment into our analyses of the various relationships among binding affinity, CO concentration, target occupancy level, and anticipated pharmacological actions. We hope that this review presents a picture of the overall landscape of CO's engagement with various targets, stimulates additional research, and helps to move the CO field in the direction of examining individual targets in the context of all of the targets and the concentration of available CO. We believe that such work will help the further understanding of the relationship of CO concentration and its pathophysiological functions and the eventual development of CO-based therapeutics. SIGNIFICANCE STATEMENT: The further development of carbon monoxide (CO) as a therapeutic agent will significantly rely on the understanding of CO's engagement with therapeutically relevant targets of varying affinity. This review critically examines the literature by quantitatively analyzing the intricate relationships among targets, target affinity for CO, CO level, and the affinity state of carboxyhemoglobin and provide a holistic approach to examining the molecular mechanism(s) of action for CO.
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Produtos Biológicos , Monóxido de Carbono , Monóxido de Carbono/metabolismo , Monóxido de Carbono/farmacologia , Humanos , Transdução de SinaisRESUMO
The pathophysiological roles of the endogenous signaling molecule, carbon monoxide (CO), have been extensively studied and validated in cell culture and animal models. Further, evidence supporting the therapeutic effects of CO in various human diseases has been mounting over the last two decades. Along this line, there has been intensive interest in developing various delivery forms including CO gas, CO in solution, metal-carbonyl complexes widely known as CO-releasing molecules (CO-RMs), and organic CO prodrugs. Among them, two ruthenium-based carbonyl complexes, CORM-2 and -3, occupy a very special place because they have been used in over 500 published studies. One of the mechanisms for CO's actions is known to be through attenuation of oxidative stress and regulation of production of reactive oxygen species (ROS). For this reason, it is important that CO delivery forms do not have intrinsic chemical redox properties. Herein, we describe our findings of catalase-like activities of CORM-2 and -3 in a CO-independent fashion, leading to the rapid degradation of hydrogen peroxide (H2O2) in PBS buffer (pH = 7.4) and in cell culture media. Further, we have found that CORM-2 and CORM-3 possess potent radical scavenging abilities. We have also studied two other widely used CO donors: CORM-401 and CORM-A1. Both showed chemical reactivity with ROS, but to a lesser degree than CORM-2 and -3. Because of the central role of ROS in some of the proposed mechanisms of actions for CO biology, the discovery of intrinsic chemical redox properties for these CO-RMs means that additional attention in designing proper controls is needed in future biological experiments using these CO-RMs for their CO-donating functions. Further, much more work is needed to understand the true implications of the chemical reactivity of these CO-RMs in cell-culture and animal-model studies of CO biology.
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Efficient white light-emitting diodes (LEDs) with an efficacy of 200 lm W-1 are much desirable for lighting and displays. The phosphor-based LEDs in use today for display applications offer poor color saturation. Intensive efforts have been made to replace the phosphor with quantum-dot-based downconverters, but the efficiency and stability of these devices are still in their infancy. Quantum rods (QRs), nanoparticles with an elongated shape, show superior properties such as relatively larger Stokes shifts, polarized emission, and high light out-coupling efficiency in the solid-state. However, these QRs usually suffer from poor optical quality for PL wavelengths < 550 nm. Herein, a gradient alloyed CdSe/Znx Cd1- x S/ZnS and CdSe/CdS/ZnS core/shell/shell QR downconverters showing high efficacy LEDs covering a wide color gamut are reported. These QRs show high stability and a precisely tunable photoluminescence peak. The engineered shell thickness suppresses energy transfer and thus maintains the high quantum yield in the solid-state (81%). These QR-based LEDs attain an efficacy of 149 lm W-1 (@10mA) and wide color gamut (118% NTSC), which is exceedingly higher than state-of-the-art quantum dots and phosphor-based on-chip LEDs.
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Hydrogen sulfide (H2S) is an endogenously produced molecule with anti-inflammatory and cytoprotective properties. We aimed to investigate for the first time if a novel, esterase-sensitive H2S-prodrug, BW-HS-101 with the ability to release H2S in a controllable manner, prevents gastric mucosa against acetylsalicylic acid-induced gastropathy on microscopic and molecular levels. Wistar rats were pretreated intragastrically with vehicle, BW-HS-101 (0.5-50 µmol/kg) or its analogue without the ability to release H2S, BW-iHS-101 prior to ASA administration (125 mg/kg, intragastrically). BW-HS-101 was administered alone or in combination with nitroarginine (L-NNA, 20 mg/kg, intraperitoneally) or zinc protoporphyrin IX (10 mg/kg, intraperitoneally). Gastroprotective effects of BW-HS-101 were additionally evaluated against necrotic damage induced by intragastrical administration of 75% ethanol. Gastric mucosal damage was assessed microscopically, and gastric blood flow was determined by laser flowmetry. Gastric mucosal DNA oxidation and PGE2 concentration were assessed by ELISA. Serum and/or gastric protein concentrations of IL-1α, IL-1ß, IL-2, IL-4, IL-6, IL-10, IL-13, VEGF, GM-CSF, IFN-γ, TNF-α, and EGF were determined by a microbeads/fluorescent-based multiplex assay. Changes in gastric mucosal iNOS, HMOX-1, SOCS3, IL1-R1, IL1-R2, TNF-R2, COX-1, and COX-2 mRNA were assessed by real-time PCR. BW-HS-101 or BW-iHS-101 applied at a dose of 50 µmol/kg protected gastric mucosa against ASA-induced gastric damage and prevented a decrease in the gastric blood flow level. H2S prodrug decreased DNA oxidation, systemic and gastric mucosal inflammation with accompanied upregulation of SOCS3, and EGF and HMOX-1 expression. Pharmacological inhibition of nitric oxide (NO) synthase but not carbon monoxide (CO)/heme oxygenase (HMOX) activity by L-NNA or ZnPP, respectively, reversed the gastroprotective effect of BW-HS-101. BW-HS-101 also protected against ethanol-induced gastric injury formation. We conclude that BW-HS-101, due to its ability to release H2S in a controllable manner, prevents gastric mucosa against drugs-induced gastropathy, inflammation and DNA oxidation, and upregulate gastric microcirculation. Gastroprotective effects of this H2S prodrug involves endogenous NO but not CO activity and could be mediated by cytoprotective and anti-inflammatory SOCS3 and EGF pathways.
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Mucosa Gástrica/efeitos dos fármacos , Sulfeto de Hidrogênio/farmacocinética , Substâncias Protetoras/farmacologia , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , DNA/metabolismo , Liberação Controlada de Fármacos , Etanol/toxicidade , Mucosa Gástrica/irrigação sanguínea , Mucosa Gástrica/patologia , Gastrite/induzido quimicamente , Gastrite/tratamento farmacológico , Gastrite/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Óxido Nítrico/metabolismo , Nitroarginina/administração & dosagem , Nitroarginina/farmacologia , Pró-Fármacos/farmacocinética , Prostaglandina-Endoperóxido Sintases/metabolismo , Prostaglandinas/metabolismo , Substâncias Protetoras/administração & dosagem , Protoporfirinas/administração & dosagem , Protoporfirinas/farmacologia , Ratos WistarRESUMO
Low-voltage fast switchable 1D and 2D Fibonacci grating (FbG), using an electrically suppressed helix ferroelectric liquid crystal (ESHFLC), with high diffraction efficiency for a super-resolution imaging system in far-field are disclosed in this paper. Specifically, the polarization-independent two-domain (0, π) structure is well designed based on photoalignment technology to maximize the total diffraction efficiency that can reach 97.4% (1st order:8.5%, 2nd order: 30%). Apart from that, the FLC gratings offer two tunable states: non-diffractive and diffractive states. Derived from the fast-response property of ferroelectric liquid crystal material, the switching speed of the 1D and 2D ESHFLC-FbG is 103µs at 4â V of the driving voltage. Furthermore, this system achieves the high-resolving power of (λ/2.25) for object detection based upon the intensity map received behind 1D ESHFLC-FbG at far-field. Contribution from the quasi-periodic FbG's special ability to translate the super-resolution information (including at evanescent wave) into the detectable far-field region. Concisely, the proposed ESHFLC-FbG can be a promising candidate for a super-resolution imaging system, superstructure fibre sensor, and other photonic applications.
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Optical devices like virtual reality (VR) headsets present challenges in terms of vergence-accommodation conflict that leads to visual fatigue for the user over time. Lenses available to meet these challenges include liquid crystal (LC) lenses, which possess a response time in the millisecond range. This response time is slow, while accessing multiple focal lengths. A ferroelectric liquid crystal (FLC) has a response time in the microsecond range. In this article, we disclose a switchable lens device having a combination of the fast FLC-based polarization rotation unit and a passive polarization-dependent LC lens. A cascaded combination of three such lens units allows access to eight different focal points quite rapidly and can be a convenient device for VR applications.
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Ruthenium-based CO-releasing molecules (CO-RMs), CORM-2 and CORM-3, have been widely used as surrogates of CO for studying its biological effects in vitro and in vivo with much success. However, several previous solution-phase and in vitro studies have revealed the ability of such CO-RMs to chemically modify proteins and reduce aromatic nitro groups due to their intrinsic chemical reactivity under certain conditions. In our own work of studying the cytoprotective effects of CO donors, we were in need of assessing chemical factors that could impact the interpretation of results from CO donors including CORM-2,3 in various in vitro assays. For this, we examined the effects of CORM-2,3 toward representative reagents commonly used in various bioassays including resazurin, tetrazolium salts, nitrites, and azide-based H2S probes. We have also examined the effect of CORM-2,3 on glutathione disulfide (GSSG), which is a very important redox regulator. Our studies show the ability of these CO-RMs to induce a number of chemical and/or spectroscopic changes for several commonly used biological reagents under near-physiological conditions. These reactions/spectroscopic changes cannot be duplicated with CO-deleted CO-RMs (iCORMs), which are often used as negative controls. Furthermore, both CORM-2 and -3 are capable of consuming and reducing GSSG in solution. We hope that the results described will help in the future design of control experiments using Ru-based CO-RMs.
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Compostos Organometálicos , Rutênio , Monóxido de Carbono , Indicadores e Reagentes , NitritosRESUMO
Smart drugs, such as antibody-drug conjugates, for targeted therapy rely on the ability to deliver a warhead to the desired location and to achieve activation at the same site. Thus, designing a smart drug often requires proper linker chemistry for tethering the warhead with a vehicle in such a way that either allows the active drug to retain its potency while being tethered or ensures release and thus activation at the desired location. Recent years have seen much progress in the design of new linker activation strategies. Herein, we review the recent development of chemical strategies used to link the warhead with a delivery vehicle for preferential cleavage at the desired sites.
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Preparações Farmacêuticas , Sistemas de Liberação de Medicamentos , HumanosRESUMO
Hydrogen sulfide (H2S) is commonly referred to as the third gasotransmitter with firmly established physiological roles. Prodrug approaches have been broadly applied to deliver H2S for various applications and mechanistic studies. Since S-persulfidation and glutathionylation are known to be important in cellular signaling by sulfur species, there have been interests in developing donors of persulfide and glutathione persulfide as well. In this review, we discuss the recent development in area of prodrugs for various sulfur species.
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Sulfeto de Hidrogênio/química , Sulfeto de Hidrogênio/farmacologia , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Sulfetos/química , Sulfetos/farmacologia , Desenvolvimento de Medicamentos , Humanos , Estrutura MolecularRESUMO
Significance: Bioactive sulfur species such as hydrogen sulfide (H2S), persulfide species (R-SnSH, n ≥ 1), hydrogen polysulfide (H2Sn, n ≥ 2), sulfur dioxide (SO2), and carbon disulfide (CS2) participate in various physiological and/or pathological pathways such as vasodilation, apoptosis, inflammation, and energy metabolism regulation. The oxidation state of the individual sulfur species endows them unique biological activities. Recent Advances: There have been great strides made in achieving molecular understanding of the sulfur-signaling processes. Critical Issues: The development of various chemical tools that deliver reactive sulfur species in a controllable manner has played an important role in understanding the different roles of various sulfur species. In this review, we focus on three types of sulfur species, including persulfide, SO2, and CS2. Starting with a brief introduction of their physiological functions, we will then assess the various drug delivery strategies to generate persulfide species, SO2, and CS2 as research tools and potentially as therapeutic agents. Future Directions: Development of donors of various sulfur species that respond to distinct stimulus is critical for this field. Another key to the long-term success of this field is the identification of an area of unmet medical need that can be addressed with these sulfur species.
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Dissulfeto de Carbono/metabolismo , Pró-Fármacos/metabolismo , Sulfetos/metabolismo , Dióxido de Enxofre/metabolismo , Dissulfeto de Carbono/administração & dosagem , Dissulfeto de Carbono/farmacologia , Sistemas de Liberação de Medicamentos , Desenvolvimento de Medicamentos , Humanos , Redes e Vias Metabólicas , Oxirredução , Estresse Oxidativo , Pró-Fármacos/administração & dosagem , Pró-Fármacos/farmacologia , Transdução de Sinais , Sulfetos/administração & dosagem , Sulfetos/farmacologia , Enxofre/metabolismo , Dióxido de Enxofre/administração & dosagem , Dióxido de Enxofre/farmacologiaRESUMO
Recently, several arylnitro-based fluorescent CO probes have been reported. The design was based on CO's ability to reduce an arylnitro group for fluorescence turn-on. In this work, we assessed the response of three published arylnitro-based fluorescent CO probes, namely COFP, LysoFP-NO2, and NIR-CO toward CO from various sources. We found that only ruthenium-based CO releasing molecules (CO-RMs) were able to turn on the fluorescence while pure CO gas and CO from other sources did not turn-on the probe in the absence of ruthenium. Further experiments with different ruthenium complexes indicate that the reduction of arylnitro group requires the ruthenium carbonyl complex as an essential ingredient. As further confirmation, we also conducted the reduction of the nitro group in a p-nitrobenzamide compound and came to the same conclusion. As such, COFP and related arynitro-based probes are able to sense CORM-2 and CORM-3, but not CO in general. Our findings also indicate the need to use CO from various sources in future assessment of new CO probes.
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Previously, we reported a class of MDM2-MDM4 dimerization inhibitors that upregulate p53 and showed potent anticancer activity in animal models. However, water solubility hinders their further development. Herein we describe our effort to develop a prodrug approach that overcomes the solubility problem. The prodrug of BW-AQ-238, a potent anthraquinone analog, was made by esterification of the hydroxyl group with various natural amino acids. Cytotoxicity of these compounds toward Hela and EU-1 cells, their aqueous solubility, and the release kinetics of these prodrugs in buffer and in the presence of hydrolytic enzymes were studied. The results demonstrate that the amino acid prodrug approach significantly improved the water solubility while maintaining the potency of the parent drug.
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Aminoácidos/química , Antraquinonas/química , Pró-Fármacos/química , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Antraquinonas/metabolismo , Antraquinonas/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Meia-Vida , Humanos , Pró-Fármacos/metabolismo , Pró-Fármacos/farmacologia , Relação Estrutura-Atividade , Regulação para Cima/efeitos dos fármacosRESUMO
A bottleneck for developing CO-based therapeutics is the lack of a safe and controllable delivery form. Herein, we describe efforts toward organic CO prodrugs with dual-responsive endogenous triggers. One representative CO prodrug showed significant anti-inflammatory effects both in vitro and in a LPS-simulated systemic inflammation model. These results firmly establish such CO prodrugs as either research tools or candidate compounds for the treatment of systemic inflammation or inflammation related organ injuries.