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1.
J Colloid Interface Sci ; 605: 582-591, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34343731

RESUMO

Diabetes is a metabolic disease that is affecting an ever-increasing number of people worldwide, resulting in increased burdens on healthcare systems and societies. Constant monitoring of blood glucose levels is required to prevent serious or even deadly complications. One major challenge of diabetes management is the simple and timely administration of insulin to facilitate consistent blood glucose regulation and reduce the incidence of hypoglycemia. With this research, we construct an insulin delivery system, the delivery system is comprised of phenylboronic acid based fluorescent probes, which is used as glucose responsive linkers, mesoporous silica nanoparticles providing an insulin reservoir, and zinc oxide nanoparticles used as gate keepers. The system with glucose sensitive responsive linker exhibits controlled release of insulin under high glucose concentrations, providing prolonged blood glucose regulation and no risks of hypoglycemia. Furthermore, the system is combined with a hyaluronic-acid based microneedle patch, which exhibit efficient skin penetration for transdermal delivery. With our system, the nanoparticles provide outstanding in vivo glucose regulation when administrated by subcutaneous injection or via transdermal microneedle patch. We anticipate that our biocompatible smart glucose responsive microneedle patch (SGRM patch) will facilitate the development of clinically useful systems.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Hipoglicemia , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Humanos , Hipoglicemia/tratamento farmacológico , Insulina , Agulhas
2.
Bioorg Med Chem Lett ; 51: 128371, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34534673

RESUMO

Malignant gliomas are the most common brain tumors, with generally dismal prognosis, early clinical deterioration and high mortality. Recently, 2-aminoquinoline scaffold derivatives have shown pronounced activity in central nervous system disorders. We herein reported a series of 2-aminoquinoline-3-carboxamides as novel non-alkylator anti-glioblastoma agents. The synthesized compounds showed comparable activity to cisplatin against glioblastoma cell line U87 MG in vitro. Among them, we found that 6a displayed good inhibitory activity against A172 and U118 MG glioblastoma cell lines and induced cell cycle arrest in the G2/M phase and apoptosis in U87 MG by flow cytometry analysis. Additionally, 6a displayed low cytotoxicity to several normal human cell lines. In silico study showed 6a had promising physicochemical properties and was predicted to cross the blood-brain barrier. Moreover, preliminary structure-activity relationships are also investigated, shedding light on further modifications towards more potent agents on this series of compounds. Our results suggest this compound has a promising potential as an anti-glioblastoma agent with a differential effect between tumor and non-malignant cells.

3.
Anal Methods ; 13(27): 3012-3016, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34212163

RESUMO

By combining a Hill-type pH probe and a pH-insensitive naphthalimide fluorophore, we synthesized a FRET-based ratiometric pH probe (PHHF), exhibiting a reduced pH transition width, representing a unique approach for development of sensitive probes for detection of biorelevant pH changes.


Assuntos
Corantes Fluorescentes , Naftalimidas , Células HeLa , Humanos , Concentração de Íons de Hidrogênio
4.
Chem Commun (Camb) ; 57(61): 7553-7556, 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34240730

RESUMO

Fluorophores with photo-modulatory fluorescence properties are valuable for cutting-edge localization microscopy. The existing probes are either photo-activatable, or photo-switchable, but not both. We report a probe (DH-SiR), a leuco-dye obtained by reduction of Si-rhodamine, with both photo-activatable and photo-switchable fluorescence. The potential for super-resolution microscopy was showcased.

5.
J Agric Food Chem ; 69(27): 7526-7533, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34212716

RESUMO

OfChi-h, a lepidopteran-exclusive glycoside hydrolase family 18 (GH18) chitinase from the agricultural insect pest Ostrinia furnacalis, is a promising molecular target candidate for pest control and management. Berberine (BER), a traditional Chinese medicine, binds to a wide variety of glycosyl hydrolases via an identical mechanism, showing potential as a pesticide lead compound. In this work, we found that BER was a moderate inhibitor of OfChi-h with a Ki of 16.1 µM. To improve its efficacy, a series of BER derivatives featuring an ester bond linked to an aromatic or heterocyclic aromatic ring at the 9-position were designed and evaluated as effective OfChi-h inhibitors. The most potent compound, compound 19e with a nicotinate group, exhibited a Ki of 0.093 µM. Molecular docking analysis suggested that the common binding mode of BER derivatives featured a network of π-π stacking and electrostatic interactions and that the group at the 9-position enhanced the van der Waals and hydrogen bonding interactions. Administration of the BER derivative 19c to 4th-instar O. furnacalis larvae in an artificial diet led to their impaired growth and metamorphosis. This work provides a new starting point for the modification of BER for use in pest control.


Assuntos
Berberina , Quitinases , Mariposas , Animais , Ésteres , Simulação de Acoplamento Molecular
6.
Bioorg Med Chem Lett ; 44: 128114, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34015501

RESUMO

Crop pathogens reduce the yield and quality of agricultural production. The development of new fungicides will help to sustain this protection and overcome fungicide resistance. Sydnone is a kind of mesoionic, which has a wide range of biological activities. The application of sydnones in agriculture is less, and the study of these compounds will lead to the discovery of new active compounds. In this study, we designed and synthesized a series of noval sydnone mesoionic derivatives by active substructure splicing. All compounds were characterized using 1H and 13C NMR spectroscopy. Among them, trifluoromethyl compound D17 showed good bioactivity against Pseudoperonospora cubensis (EC50 = 49 mg L-1) in vivo, the activity was similar to that of the control Kresoxim-methyl (EC50 = 44 mg L-1). However, the target of these compounds should not only be tyrosinase, and the mode of action needs to be further studied. In addition, the structure-activity relationship indicated that the trifluoromethyl group was more beneficial for antifungal activity. This is the first report that fluorine-containing N(3)-benzyl sydnone compounds have good fungicidal activity. These results will provide a basis for the development of sydnone mesoionic as new lead fungicidal agents.

7.
Bioorg Med Chem Lett ; 46: 128120, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34015502

RESUMO

Triflumezopyrim (TFM) is a new mesoionic insecticide developed by DuPont. Like other neonicotinoid insecticides, it binds to the orthosteric site of the nicotinic acetylcholine receptor (nAChR), but the binding mode has not been reported. Nicotinic acetylcholine binding proteins (nAChBPs) are ideal alternative structure for nAChRs. In this study, molecular docking, molecular dynamics (MD) simulations, binding free energy calculation, and per-residue binding free energy decomposition were used to study the binding modes of TFM and other 12 mesoionic insecticides. By comparing the binding free energy and the insecticidal activity, it was found that the sub-pocket around the benzyl group of the mesoionic insecticide is the key area for maintaining its activity, which is composed of A: Val116, A: Met124, A: Ile126, B: Trp155 and B: Val156. In order to verify the druggability of the sub-pocket, a series of iminosydnone compounds were designed and synthesized based on the structure of the sub-pocket. The lethality rate of compound 1 against Mythimna separata were 100% at 500 mg/L. Our research provides a basis for designing new mesoionic insecticides based on structure.

8.
Int J Pharm ; 603: 120730, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34029662

RESUMO

Photodynamic therapy (PDT) efficacy has been severely limited by the hypoxia in tumor microenvironment. A multitherapy modality was developed, integrating the advantages of each therapy and a nanocarrier: PDT and PDT-induced hypoxia-activated chemotherapy. Following PDT-induced hypoxia augmented in the periphery of the tumors, chemotherapy was locally activated. To this end, new indocyanine green (IR820) and a hypoxia-activated prodrug tirapazamine (TPZ) were loaded in glutathione (GSH) decomposable mesoporous organic silica nanoparticles (GMONs), tethered by hyaluronic acid (HA). This nanohybrid showed a tendency to accumulate and be retained in tumors, due to passive and active targeting. The IR820 produced singlet oxygen (1O2) under near-infrared (NIR) laser irradiation and concomitantly tumorous abnormality exacerbated hypoxia. TPZ-mediated hypoxia-activated chemotherapy acted to kill more tumor cells. In vivo results indicated that the tumor inhibition rate of dual-loaded nanohybrids was up to 76% under NIR laser irradiation. The immunofluorescence staining of tumor slices demonstrated that the superficial part of tumors experienced exacerbated hypoxia with laser irradiation, resulting in TPZ exerting powerful chemotherapy effects. This nanohybrid is expected to be valuable as spatiotemporally specific therapy for cancer.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Linhagem Celular Tumoral , Glutationa , Humanos , Hipóxia , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Tirapazamina/uso terapêutico , Microambiente Tumoral
9.
Acta Biomater ; 128: 435-446, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33862284

RESUMO

Multi-modal combination therapy has attracted great attention, owing to the unsatisfactory therapeutic efficacy of conventional chemotherapy. Mesoporous silica-coated gold nanorods possess great potential in photothermal therapy and drug delivery. In this work, we fabricate a dual-responsive nanohybrid for combination treatment of the malignant tumor. In this system, gold nanorods are coated with the degradable mesoporous silica, and the chemotherapy drug doxorubicin (DOX) and photosensitizer (IR820) are co-loaded inside the pores of the silica. The encapsulation of hyaluronic acid (HA) endow the nanohybrids with mammary carcinoma targeting ability and better biocompatibility, owning to CD44+ receptor overexpressed in some cancer cells. As-prepared nanohybrids exhibit high responsiveness to a high glutathione (GSH) level and degrade rapidly in the presence of hyaluronidase (HAase) and GSH after endocytosis by 4T1 cells, allowing the efficient release of loaded DOX and IR 820 in tumor sites. Interestingly, near-infrared (NIR) laser not only triggers the generation of reactive oxygen species, but also remarkable photothermal efficacy originating from GNRs. Therefore, upon the irradiation of 808 nm NIR light, the combinatorial photodynamic, photothermal and chemotherapy is achieved, accordingly leading to a highly efficient antitumor outcome in vitro and in vivo. This strategy provides an ideal approach to constructing multimodal cancer therapy system. STATEMENT OF SIGNIFICANCE: • Dual-responsive nanohybrids for combinatorial therapy of breast cancer. • The nanohybrids exhibit both HAase and GSH stimuli-responsive behavior. • The nanohybrids exhibit light-activated PDT/PTT/chemotherapy. • The nanohybrids show good biosafety for potential clinical application.


Assuntos
Neoplasias da Mama , Nanotubos , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Feminino , Ouro , Humanos , Fototerapia , Dióxido de Silício
10.
Soft Matter ; 17(5): 1184-1188, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33527954

RESUMO

A series of short intrinsically disordered polypeptide conjugated oligonucleotides (IDPOCs) were rationally developed and assembled into well-defined nanospheres. The nanospheres exhibited excellent reversible thermoresponsive regulation of their contraction and expansion. Furthermore, the nanospheres showed biocompatibility, drug encapsulation and effective cellular uptake.


Assuntos
Nanosferas , Oligonucleotídeos , Peptídeos , Temperatura
11.
Phytochemistry ; 184: 112657, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33461047

RESUMO

Plants are known to develop a multi-faceted innate immune system for pathogenic defense. Systemic acquired resistance (SAR) and induced systemic resistance (ISR) are the two main pathways. Many chemical inducers known as plant activators that activate innate immunity to defend against pathogens have been discovered. Currently, the exploitation of new plant activators is mainly done to develop analogs of salicylic acid as SAR-signaling molecules; however, the ISR pathway is hardly investigated for new plant activators. Based on recent studies on 1-methyl pyrazolo [3,4-d]pyrimidine bioactivity and ATP-induced resistance to biotrophic and necrotrophic pathogens, a new lead compound, 1-methyl-4-amino-pyrazolo [3,4-d]pyrimidine, was obtained as a new scaffold of plant activators for possible inducing ISR immunity system. Additionally, fluorine atom plays an important role in the design and development of new pesticides due to the unique physical chemistry effect, a series of pyrazolo [3,4-d]pyrimidine derivatives were designed and synthesized. Several compounds showed good broad-spectrum induced resistance in vivo, but there was no direct antibacterial activity in vitro. Notably, the introduction of fluorine atom at the para-position of the benzene ring greatly enhanced the induction activity of P1d both involved in SAR and ISR pathways, which implied the inducing resistance both in defending pathogens and insects.


Assuntos
Doenças das Plantas , Plantas , Sistema Imunitário , Pirimidinas/farmacologia , Ácido Salicílico
12.
Free Radic Biol Med ; 164: 13-19, 2021 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-33418107

RESUMO

Nitric oxide donors (NODs) are indispensable in biological research and disease treatment. NODs had been utilized to treat cardiovascular diseases in clinic and many others are under trial. Thiols are typically required for these donors to release NO. Yet, their mechanism is complex and often lead to resistance. Herein, we reported that N-nitrosated electron-deficient dyes are capable of NO release with one-electron reduction. A fluorophore is generated simultaneously, whose fluorescence is harnessed to monitor the profile of NO release. Through electrochemical and spectral studies, NOD f3 was found to exhibit good biocompatibility and high reduction efficiency and its potentials in cell-protection in oxygen and glucose deprivation (OGD) models were showcased with endothelial cells. This work aims at offering a new approach to design reduction-triggered NOD, which have therapeutic potentials in ischemia-reperfusion.


Assuntos
Óxido Nítrico , Traumatismo por Reperfusão , Elétrons , Células Endoteliais , Humanos , Isquemia , Reperfusão , Traumatismo por Reperfusão/prevenção & controle
13.
Chem Soc Rev ; 50(1): 9-38, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33169731

RESUMO

Indicator displacement assays (IDAs) offer a unique and innovative approach to molecular sensing. IDAs can facilitate the detection of a range of biologically/environmentally important species, provide a method for the detection of complex analytes or for the determination and discrimination of unknown sample mixtures. These attributes often cannot be achieved by traditional molecular sensors i.e. reaction-based sensors/chemosensors. The IDA pioneers Inouye, Shinkai, and Anslyn inspired researchers worldwide to develop various extensions of this idea. Since their early work, the field of indicator displacement assays has expanded to include: enantioselective indicator displacement assays (eIDAs), fluorescent indicator displacement assays (FIDAs), reaction-based indicator displacement assays (RIAs), DimerDye disassembly assays (DDAs), intramolecular indicator displacement assays (IIDAs), allosteric indicator displacement assay (AIDAs), mechanically controlled indicator displacement assays (MC-IDAs), and quencher displacement assays (QDAs). The simplicity of these IDAs, coupled with low cost, high sensitivity, and ability to carry out high-throughput automation analysis (i.e., sensing arrays) has led to their ubiquitous use in molecular sensing, alongside the other common approaches such as reaction-based sensors and chemosensors. In this review, we highlight the various design strategies that have been used to develop an IDA, including the design strategies for the newly reported extensions to these systems. To achieve this, we have divided this review into sections based on the target analyte, the importance of each analyte and then the reported IDA system is discussed. In addition, each section includes details on the benefit of the IDAs and perceived limitations for each system. We conclude this Tutorial Review by highlighting the current challenges associated with the development of new IDAs and suggest potential future avenues of research.

14.
Spectrochim Acta A Mol Biomol Spectrosc ; 245: 118907, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32932032

RESUMO

Fluorophores with a minimal push-pull backbone are actively pursued due to their potentials in biological labelling. Herein a series of structurally-thrifty and visible-absorbing fluorophores (SDXs) were successfully constructed following the D'D-π-A design strategy, in which a secondary donor (D') was introduced in conjugation with the donor (D) to enhance its electron donating capability. For a very small scaffold, SDXs exhibit a surprisingly long-wavelength absorption band in the visible spectral range (λabs = 420 nm) and a strong green fluorescence emission (λem = 530 nm) with a fluorescence quantum yield up to 0.84. Notably, fluorescence of SDXs was quenched in hydrogen-bonding solvents, e.g. MeOH and H2O. This phenomenon renders SDXs feasibility for imaging of cellular non-hydrogen-bonding microenvironment, as demonstrated with BEAS-2B cells. These results proved that the D'D-π-A is a powerful design strategy to construct novel structurally-thrifty fluorophores.

15.
J Agric Food Chem ; 68(47): 13584-13593, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33151676

RESUMO

Chitinases are the glycosyl hydrolase for catalyzing the degradation of chitin and play an indispensable role in bacterial pathogenesis, fungal cell wall remodeling, and insect molting. Thus, chitinases are attractive targets for therapeutic drugs and pesticides. Here, we present a strategy of developing a novel chemotype of chitinase inhibitors by the construction of planar heterocycles that can stack with conserved aromatic residues. The rational design, guided by crystallographic analysis and docking results, leads to a series of dipyridopyrimidine-3-carboxamide derivatives as chitinase inhibitors. Among them, compound 6t showed the most potent activity against bacterial chitinase SmChiB and insect chitinase OfChi-h, with a Ki value of 0.14 and 0.0056 µM, respectively. The strong stacking interaction of compound 6p with Trp99 and Trp220 found in the SmChiB-6p co-crystal structure verifies the feasibility of our design. Our results provide novel insights into developing potent chitinase inhibitors for pathogen and pest control.


Assuntos
Quitinases , Simulação de Acoplamento Molecular , Quitina , Inibidores Enzimáticos/farmacologia , Controle de Pragas , Raios X
16.
J Enzyme Inhib Med Chem ; 35(1): 1937-1943, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33167737

RESUMO

Glycoside hydrolase family 18 (GH18) chitinases play an important role in various organisms ranging from bacteria to mammals. Chitinase inhibitors have potential applications as pesticides, fungicides, and anti-asthmatics. Berberine, a plant-derived isoquinoline alkaloid, was previously reported to inhibit against various GH18 chitinases with only moderate K i values ranging between 20 and 70 µM. In this report, we present for the first time the berberine-complexed crystal structure of SmChiB, a model GH18 chitinase from the bacterium Serratia marcescens. Based on the berberine-binding mode, a hydrophobic cavity-based optimisation strategy was developed to increase their inhibitory activity. A series of berberine derivatives were designed and synthesised, and their inhibitory activities against GH18 chitinases were evaluated. The compound 4c showed 80-fold-elevated inhibitory activity against SmChiB and the human chitinase hAMCase with K i values at the sub-micromolar level. The mechanism of improved inhibitory activities was proposed. This work provides a new strategy for developing novel chitinase inhibitors.


Assuntos
Berberina/química , Quitinases/antagonistas & inibidores , Inibidores Enzimáticos/química , Sequência de Aminoácidos , Berberina/metabolismo , Inibidores Enzimáticos/metabolismo , Humanos , Interações Hidrofóbicas e Hidrofílicas , Simulação de Acoplamento Molecular , Ligação Proteica , Serratia marcescens/enzimologia , Relação Estrutura-Atividade
17.
J Mater Chem B ; 8(47): 10686-10699, 2020 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-33156324

RESUMO

Near-infrared dyes possess the qualities of lower interference with biological autofluorescence, low photon scattering, and deep tissue penetration, and are being increasingly involved in the development of biomaterials for sensing and precision medicine. However, dyes usually suffer from the disadvantages of poor water solubility and photobleaching, factors that limit their application in vivo. The introduction of supramolecular ensembles can provide an ideal solution. This review presents recently developed supramolecular ensembles modified by near-infrared dyes. Compared with small-molecule fluorophores, the specific size of a supramolecular-based fluorophore endows it with longer circulation time in the bloodstream, increasing its chances of reaching a specific target. In addition, the construction of supramolecule-based fluorophores with versatile functions can be achieved by simple encapsulation or doping, instead of by complicated chemical synthesis. Thus, supramolecular-complex-based fluorophores offer high potential in diagnosis and therapy. This review outlines four different species of near-infrared dye based ensembles in terms of their method of formation, including simple encapsulation or doping and copolymerisation. Recently, a new technology has employed modified fluorophores for in situ self-assembly that form supramolecular ensembles at a specific position, thus solving the problem of poor uptake of nanoparticles by cells, and is included in this review. Finally, the future of this field is considered.


Assuntos
Corantes Fluorescentes/síntese química , Corantes Fluorescentes/metabolismo , Nanopartículas/química , Nanopartículas/metabolismo , Imagem Óptica/métodos , Animais , Membrana Celular/química , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Corantes Fluorescentes/administração & dosagem , Humanos , Nanopartículas/administração & dosagem , Fótons , Polímeros/administração & dosagem , Polímeros/síntese química , Polímeros/metabolismo , Espectroscopia de Luz Próxima ao Infravermelho/métodos
18.
Theranostics ; 10(19): 8691-8704, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32754272

RESUMO

Rationale: Nanoscale vehicles responsive to abnormal variation in tumor environment are promising for use in targeted delivery of therapeutic drugs specifically to tumor sites. Herein, we report the design and fabrication of self-accelerating H2O2-responsive plasmonic gold nanovesicles (GVs) encapsulated with tirapazamine (TPZ) and glucose oxidase (GOx) for synergistic chemo/starving therapy of cancers. Methods: Gold nanoparticles were modified with H2O2-responsive amphiphilic block copolymer PEG45-b-PABE330 by ligand exchange. The TPZ and GOx loaded GVs (TG-GVs) were prepared through the self-assembly of PEG45-b-PABE330 -grafted nanoparticles together with TPZ and GOx by solvent displacement method. Results: In response to H2O2 in tumor, the TG-GVs dissociate to release the payloads that are, otherwise, retained inside the vesicles for days without noticeable leakage. The released GOx enzymes catalyze the oxidation of glucose by oxygen in the tumor tissue to enhance the degree of hypoxia that subsequently triggers the reduction of hypoxia-activated pro-drug TPZ into highly toxic free radicals. The H2O2 generated in the GOx-catalyzed reaction also accelerate the dissociation of vesicles and hence the release rate of the cargoes in tumors. The drug-loaded GVs exhibit superior tumor inhibition efficacy in 4T1 tumor-bearing mice owing to the synergistic effect of chemo/starvation therapy, in addition to their use as contrast agents for computed tomography imaging of tumors. Conclusion: This nanoplatform may find application in managing tumors deeply trapped in viscera or other important tissues that are not compatible with external stimulus (e.g. light).


Assuntos
Neoplasias da Mama/tratamento farmacológico , Glucose Oxidase/administração & dosagem , Ouro/química , Peróxido de Hidrogênio/metabolismo , Tirapazamina/administração & dosagem , Animais , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Sinergismo Farmacológico , Feminino , Glucose Oxidase/química , Glucose Oxidase/farmacologia , Humanos , Nanopartículas Metálicas , Camundongos , Tirapazamina/química , Tirapazamina/farmacologia , Tomografia Computadorizada por Raios X , Hipóxia Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Chem Commun (Camb) ; 56(64): 9067-9078, 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32613958

RESUMO

Fluorescent probes find widespread applications in chemical analysis, biosensing, and disease diagnosis and are also the cornerstones of many cutting-edge biotechnologies. Yet, the numerous probes developed thus far are actually based on a handful of probe design principles. In this article, we wish to summarize the recent progress of the field toward the use of a novel "covalent-assembly" principle for probe design.


Assuntos
Desenho de Fármacos , Corantes Fluorescentes/química , Linhagem Celular Tumoral , Humanos , Estrutura Molecular
20.
Chem Sci ; 11(5): 1394-1403, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-34123264

RESUMO

Fluorescent probes for nitric oxide (NO), or more frequently for its oxidized surrogate dinitrogen trioxide (N2O3), have enabled scientists to study the contributions of this signaling molecule to many physiological processes. Seeking to improve upon limitations of other probes, we have developed a family of fluorescent probes based on a 2-amino-3'-dialkylaminobiphenyl core. This core condenses with N2O3 to form benzo[c]cinnoline structures, incorporating the analyte into the newly formed fluorophore, which results in product fluorescence with virtually no background contribution from the initial probe. We varied the substituents in the core in order to optimize both the reactivity of the probes with N2O3 and their cinnoline products' fluorescence wavelengths and brightness. The top candidates were then applied to cultured cells to verify that they could respond to NO within cellular milieus, and the top performer, NO530, was compared with a "gold standard" commercial probe, DAF-FM, in a macrophage-derived cell line, RAW 264.7, stimulated to produce NO. NO530 demonstrated similar or better sensitivity and higher selectivity for NO than DAF, making it an attractive potential alternative for NO tracking in various applications.

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