Copper-Catalyzed Enantioselective Synthesis of Spirohydroindoles by Ethoxyformylmethylene Oxindole and Iminoester 1,3-Dipole Cycloaddition: An Examination of Associated Biological Activities.

A highly enantioselective 1,3-dipolar cycloaddition of ethoxyformylmethylene oxindole with iminoesters has been achieved using the Cu(I)-(S,Sp)-Ph Phosferrox catalytic system, generating a series of chiral spiro[pyrrolidin-3,3'-oxindole] compounds with four consecutive stereocenters, including a spirocycle quaternary center (71%-99% yield, up to >20:1 dr and 95:5 er). The compounds exhibited good inhibitory activity against Valsa mali (V.m.), Fusarium oxysporium (F.o.), and Alternaria brassicae (A.b.).

Fluorescent small molecule donors.

Small molecule donors (SMDs) play subtle roles in the signaling mechanism and disease treatments. While many excellent SMDs have been developed, dosage control, targeted delivery, spatiotemporal feedback, as well as the efficiency evaluation of small molecules are still key challenges. Accordingly, fluorescent small molecule donors (FSMDs) have emerged to meet these challenges. FSMDs enable controllable release and non-invasive real-time monitoring, providing significant advantages for drug development and clinical diagnosis. Integration of FSMDs with chemotherapeutic, photodynamic or photothermal properties can take full advantage of each mode to enhance therapeutic efficacy. Given the remarkable properties and the thriving development of FSMDs, we believe a review is needed to summarize the design, triggering strategies and tracking mechanisms of FSMDs. With this review, we compiled FSMDs for most small molecules (nitric oxide, carbon monoxide, hydrogen sulfide, sulfur dioxide, reactive oxygen species and formaldehyde), and discuss recent progress concerning their molecular design, structural classification, mechanisms of generation, triggered release, structure-activity relationships, and the fluorescence response mechanism. Firstly, from the large number of fluorescent small molecular donors available, we have organized the common structures for producing different types of small molecules, providing a general strategy for the development of FSMDs. Secondly, we have classified FSMDs in terms of the respective donor types and fluorophore structures. Thirdly, we discuss the mechanisms and factors associated with the controlled release of small molecules and the regulation of the fluorescence responses, from which universal guidelines for optical properties and structure rearrangement were established, mainly involving light-controlled, enzyme-activated, reactive oxygen species-triggered, biothiol-triggered, single-electron reduction, click chemistry, and other triggering mechanisms. Fourthly, representative applications of FSMDs for trackable release, and evaluation monitoring, as well as for visible in vivo treatment are outlined, to illustrate the potential of FSMDs in drug screening and precision medicine. Finally, we discuss the opportunities and remaining challenges for the development of FSMDs for practical and clinical applications, which we anticipate will stimulate the attention of researchers in the diverse fields of chemistry, pharmacology, chemical biology and clinical chemistry. With this review, we hope to impart new understanding thereby enabling the rapid development of the next generation of FSMDs.

Developing NIR xanthene-chalcone fluorophores with large Stokes shifts for fluorescence imaging.

A series of novel near-infrared (NIR) xanthene-chalcone fluorophores were constructed through a modular synthesis with the electron-donating xanthene moiety and the electron-withdrawing chalcone moiety. These fluorophores are convenient for fluorescence imaging in living cells, benefiting from their NIR emissions (650-710 nm), large Stokes shifts (>100 nm), moderate quantum yields and low cytotoxicity. The substituted hydroxyl group of the xanthene-chalcone fluorophore HCA-E facilitates the development of multifunctional fluorescent probes. As an example, a highly sensitive and selective probe N-HCA-E for glutathione (GSH) detection was developed based on the fluorophore HCA-E. A 4-nitrobenzenesulfonyl (4-Ns) group was introduced to cage the hydroxyl group of HCA-E, which was used as a selective recognition site for the thiol of GSH and an effective fluorescence quencher. Probe N-HCA-E revealed NIR "turn-on" fluorescence (709 nm) for endogenous and exogenous GSH detection in lysosomes with a large Stokes shift (129 nm) and high anti-interference ability.

Design, Synthesis, Antifungal Evaluation, Structure-Activity Relationship (SAR) Study, and Molecular Docking of Novel Spirotryprostatin A Derivatives.

Phytopathogenic fungi cause plant diseases and economic losses in agriculture. To efficiently control plant pathogen infections, a total of 19 spirotryprostatin A derivatives and 26 spirooxindole derivatives were designed, synthesized, and tested for their antifungal activity against ten plant pathogens. Additionally, the intermediates of spirooxindole derivatives were investigated, including proposing a mechanism for diastereoselectivity and performing amplification experiments. The bioassay results demonstrated that spirotryprostatin A derivatives possess good and broad-spectrum antifungal activities. Compound 4d exhibited excellent antifungal activity in vitro, equal to or higher than the positive control ketoconazole, against Helminthosporium maydis, Trichothecium roseum, Botrytis cinerea, Colletotrichum gloeosporioides, Fusarium graminearum, Alternaria brassicae, Alternaria alternate, and Fusarium solan (MICs: 8-32 µg/mL). Compound 4k also displayed remarkable antifungal activity against eight other phytopathogenic fungi, including Fusarium oxysporium f. sp. niveum and Mycosphaerella melonis (MICs: 8-32 µg/mL). The preliminary structure-activity relationships (SARs) were further discussed. Moreover, molecular docking studies revealed that spirotryprostatin A derivatives anchored in the binding site of succinate dehydrogenase (SDH). Therefore, these compounds showed potential as natural compound-based chiral fungicides and hold promise as candidates for further enhancements in terms of structure and properties.

The use of Treatment and Education of Autistic and Related Communication Handicapped Children in schools to improve the ability of children with autism to complete tasks independently: A single-case meta-analysis.

OBJECTIVE: To investigate the effectiveness of a Treatment and Education of Autistic and Related Communication Handicapped Children (TEACCH) intervention in schools for improving independent task performance in children with autism spectrum disorders (ASD). METHODS: We screened relevant studies published up to December 2022 from Web of science, ERIC, PsycINFO and other databases using predefined inclusion/exclusion criteria to identify suitable intervention studies for meta-analysis. Tau-U effect sizes were calculated for each A-B comparison extracted from the included experiments. Moderated analyses were conducted to examine the type of intervention (independent variable), intervention target behaviours (dependent variable), participant characteristics, setting characteristics and intervener characteristics. RESULTS: A total of 14 studies (38 participants) met the criteria and were included in the meta-analysis. The analysis results showed that TEACCH had a significant intervention effect, and the overall intervention effect size was Tau-U = 0.85[0.77, 0.91]. There were significant differences in the intervention target behaviour variables (p < 0.01), limited variation in the intervention type variables, but no differences in participant characteristics, setting characteristics and intervenor characteristics. CONCLUSION: The use of TEACCH is effective in improving independent task completion in children with ASD and provides evidence-based recommendations for its extended use in schools.

Visual monitoring of biocatalytic processes using small molecular fluorescent probes: strategies-mechanisms-applications.

Real-time monitoring of biocatalytic-based processes is significantly improved and simplified when they can be visualized. Visual monitoring can be achieved by integrating a fluorescent unit with the biocatalyst. Herein, we outline the design strategies of fluorescent probes for monitoring biocatalysis: (1) probes for monitoring biocatalytic transfer: γ-glutamine is linked to the fluorophore as both a recognition group and for intramolecular charge transfer (ICT) inhibition; the probe is initially in an off state and is activated via the transfer of the γ-glutamine group and the release of the free amino group, which results in restoration of the "Donor-π-Acceptor" (D-π-A) system and fluorescence recovery. (2) Probes for monitoring biocatalytic oxidation: a propylamine is connected to the fluorophore as a recognition group, which cages the hydroxyl group, leading to the inhibition of ICT; propylamine is oxidized and subsequently ß-elimination occurs, resulting in exposure of the hydroxyl group and fluorescence recovery. (3) Probes for monitoring biocatalytic reduction: a nitro group attached to a fluorophore as a fluorescence quenching group, this is converted to an amino group by catalytic reduction, resulting in fluorescence recovery. (4) Probes for monitoring biocatalytic hydrolysis: ß-D-galactopyranoside or phosphate acts as a recognition group attached to hydroxyl groups of the fluorophore; the subsequent biocatalytic hydrolysis reaction releases the hydroxyl group resulting in fluorescence recovery. Following these 4 mechanisms, fluorophores including cyanine, coumarin, rhodamine, and Nile-red, have been used to develop systems for monitoring biocatalytic reactions. We anticipate that these strategies will result in systems able to rapidly diagnose and facilitate the treatment of serious diseases.

Discovery and Structural Optimization of 1,2,3,4-Tetrahydro-ß-carbolines as Novel Reactive Oxygen Species Inducers for Controlling Intractable Plant Bacterial Diseases.

Nowadays, reactive oxygen species (ROS) have been acknowledged as promising bactericidal targets against pesticide-resistant bacteria. Herein, to further excavate more excellent ROS inducers, simple 1,2,3,4-tetrahydro-ß-carboline derivatives containing a 3-aminopropanamide moiety were prepared and assessed for their antibacterial potency. Notably, three promising compounds displayed significant antibacterial potency. Compound I29 exhibits excellent in vitro bioactivity, with an EC50 value of 5.73 µg/mL, and admirable in vivo activities (protective activity of 55.74% and curative activity of 65.50%) toward Xanthomonas oryzae pv. oryzae. Compound I16 has good activity in vitro, with an EC50 of 3.43 µg/mL, and outstanding bioactivities in vivo (protective activity of 92.50% and curative activity of 59.68%) against Xanthomonas axonopodis pv. citri. Compound I6 shows excellent in vitro bioactivity (EC50 = 2.86 µg/mL) and significant protective activity (94.02%) for preventing Pseudomonas syringae pv. actinidiae. Antibacterial mechanism investigations indicate that these compounds disrupt the balance of the redox system to kill bacteria. These simple 1,2,3,4-tetrahydro-ß-carboline derivatives are promising leads to the discovery of bactericidal agents.

Degradation of extracellular and membrane proteins in targeted therapy: Status quo and quo vadis.

Targeted protein degradation (TPD) strategies, such as proteolysis-targeting chimeras (PROTACs) only work for intracellular protein degradation because they involve the intracellular protein degradation machinery. Several new technologies have emerged in recent years for TPD of extracellular and membrane proteins. Even though some progress has been demonstrated in the extracellular and membrane protein degradation field, the application of these technologies is still in its infancy. In this review, we survey the therapeutic potential of existing technologies by summarizing and reviewing discoveries and hurdles in extracellular and membrane protein-of-interest (POI) degradation.

Thalidomide for Recurrence of Symptoms following HIV-Associated Cryptococcal Meningitis.

INTRODUCTION: Cryptococcal meningitis (CM) is a serious and fatal fungal infection that affects individuals infected with human immunodeficiency virus (HIV). Despite treatment, recurrence of symptoms is common and could lead to poor outcomes. Corticosteroids are not always useful in treating symptom recurrence following HIV/CM; thus, alternative therapy is needed. Thalidomide has been reported to be effective in treating symptom recurrence in several patients with HIV/CM. This retrospective study aimed to investigate the efficacy and safety of thalidomide in the treatment of symptom recurrence following HIV/CM. METHODS: Patients who were treated with thalidomide for symptom recurrence following HIV/CM were retrospectively included. Clinical outcomes and adverse events were recorded and analyzed. RESULTS: Sixteen patients admitted between July 2018 and September 2020 were included in the analysis. During a median follow-up period of 295 (166, 419) days, all patients achieved clinical improvement in a median of 7 (4, 20) days. Among them, nine (56%) achieved complete resolution of symptoms at a median of 187 (131, 253) days, including 40% (2/5) of immune reconstitution inflammatory syndrome (IRIS), 50% (3/6) of patients with elevated ICP only, and 80% (4/5) of patients with symptoms only. Seven (43%) patients experienced nine episodes of adverse events, but no severe adverse event attributable to thalidomide was observed. None of the patients withdrew from thalidomide due to adverse events. CONCLUSION: Thalidomide appears to be effective and safe in treating different types of symptom recurrence in HIV/CM. This study provides preliminary evidence supporting future randomized clinical trials to further investigate the efficacy and safety of thalidomide in treating symptom recurrence in this population.

Cancer Cell-Specific Fluorescent Prodrug Delivery Platforms.

Targeting cancer cells with high specificity is one of the most essential yet challenging goals of tumor therapy. Because different surface receptors, transporters, and integrins are overexpressed specifically on tumor cells, using these tumor cell-specific properties to improve drug targeting efficacy holds particular promise. Targeted fluorescent prodrugs not only improve intracellular accumulation and bioavailability but also report their own localization and activation through real-time changes in fluorescence. In this review, efforts are highlighted to develop innovative targeted fluorescent prodrugs that efficiently accumulate in tumor cells in different organs, including lung cancer, liver cancer, cervical cancer, breast cancer, glioma, and colorectal cancer. The latest progress and advances in chemical design and synthetic considerations in fluorescence prodrug conjugates and how their therapeutic efficacy and fluorescence can be activated by tumor-specific stimuli are reviewed. Additionally, novel perspectives are provided on strategies behind engineered nanoparticle platforms self-assembled from targeted fluorescence prodrugs, and how fluorescence readouts can be used to monitor the position and action of the nanoparticle-mediated delivery of therapeutic agents in preclinical models. Finally, future opportunities for fluorescent prodrug-based strategies and solutions to the challenges of accelerating clinical translation for the treatment of organ-specific tumors are proposed.

Accurate photoactivation monitoring via the construction of an intramolecular synergistic counteracting mechanism of FRET and IFE.

The synergistic modulation of fluorescence resonance energy transfer (FRET) and the inner filter effect (IFE) was constructed within a molecule to control the stable fluorescence intensity as the internal standard, providing a new strategy for the accurate monitoring of photoactivation.

Design, Synthesis and Bioactivity Evaluation of Novel 2-(pyrazol-4-yl)-1,3,4-oxadiazoles Containing an Imidazole Fragment as Antibacterial Agents.

Imidazole alkaloids, a common class of five-membered aromatic heterocyclic compounds, exist widely in plants, animals and marine organisms. Because of imidazole's extensive and excellent biological and pharmacological activities, it has always been a topic of major interest for researchers and has been widely used as an active moiety in search of bioactive molecules. To find more efficient antibacterial compounds, a series of novel imidazole-fragment-decorated 2-(pyrazol-4-yl)-1,3,4-oxadiazoles were designed and synthesized based on our previous works via the active substructure splicing principle, and their bioactivities were systematically evaluated both in vitro and in vivo. The bioassays showed that some of the target compounds displayed excellent in vitro antibacterial activity toward three virulent phytopathogenic bacteria, including Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac) and Pseudomonas syringae pv. actinidiae (Psa), affording the lowest EC50 values of 7.40 (7c), 5.44 (9a) and 12.85 (9a) µg/mL, respectively. Meanwhile, compound 7c possessed good in vivo protective and curative activities to manage rice bacterial leaf blight at 200 µg/mL, with control efficacies of 47.34% and 41.18%, respectively. Furthermore, compound 9a showed commendable in vivo protective and curative activities to manage kiwifruit bacterial canker at 200 µg/mL, with control efficacies of 46.05% and 32.89%, respectively, which were much better than those of the commercial bactericide TC (31.58% and 17.11%, respectively). In addition, the antibacterial mechanism suggested that these new types of title compounds could negatively impact the cell membranes of phytopathogenic bacteria cells and cause the leakage of the intracellular component, thereby leading to the killing of bacteria. All these findings confirm that novel 2-(pyrazol-4-yl)-1,3,4-oxadiazoles containing an imidazole fragment are promising lead compounds for discovering new bactericidal agents.

Targeted Protein Degradation Induced by HEMTACs Based on HSP90.

Targeted protein degradation (TPD) strategies open up new avenues for therapeutics and provide powerful tools for biological inquiry. Herein, we present a brand-new approach, termed heat shock protein 90 (HSP90)-mediated targeting chimeras (HEMTACs), to induce intracellular protein degradation by bridging a target protein to HSP90 to drive the downregulation of proteins. We successfully showcase HEMTACs for cyclin-dependent kinase 4 and 6 (CDK4/6) by using a flexible linker to connect the targeting warhead of CDK4/6 with the HSP90 ligand. Overall, our study delivers a series of evidence that HEMTACs can serve as a valuable addition to TPD strategies, most prominently proteolysis-targeting chimera technology.

Fluorescent Ligand-Based Discovery of Small-Molecule Sulfonamide Agonists for GPR120.

As a critical member of G protein-coupled receptors (GPCRs), G protein-coupled receptor 120 (GPR120) is a potential target for many physiological diseases, such as type 2 diabetes mellitus, inflammation, and obesity. Considering that small-molecule fluorescent ligands can combine the advantages of visualization, high sensitivity and selectivity, we initially undertook an effort to develop a series of fluorescent ligands to track GPR120 and establish a method to screen GPR120 agonists. The representative fluorescent ligand N1 possesses suitable optical property, equitable biological activity, and high fluorescence imaging feasibility, therefore, based on compound N1, we subsequently founded a bioluminescence resonance energy transfer (BRET) competition binding assay to screen three series of sulfonamide GPR120 agonists we developed herein. The activity evaluation results revealed that compound D5 was a potent GPR120 agonist with high activity and selectivity. Moreover, compound D5 exhibited a significant glucose-lowering effect in db/db mice, which indicates its potential application in the treatment of type 2 diabetes mellitus in vivo. It is anticipated that our fluorescent ligand-based method is a useful toolbox and will find broad applications in the discovery of small-molecule agonists for GPR120.

Development of photocontrolled BRD4 PROTACs for tongue squamous cell carcinoma (TSCC).

The catalytic properties of small-molecule proteolysis targeting chimeras (PROTACs) may lead to uncontrolled degradation. Therefore, the main disadvantages of PROTACs are non-cancer specificity and relatively high toxicity, which limit the clinical application of PROTACs. The photocontrolled PROTACs (photoPROTACs) were proposed to overcome this issue, in which they can be triggered by ultraviolet A (UVA) or visible light to induce the degradation of the target protein. Herein, we designed several photoPROTACs to cause the degradation of bromodomain-containing protein 4 (BRD4) on-demand using 365 nm light. The representative compound N2 is proved to induce the degradation of BRD4 upon irradiation. Moreover, compound N2 was successfully applied in vivo to inhibit tumor growth in a zebrafish xenograft model of skin cancer tongue squamous cell carcinoma (TSCC) in a photocontrol manner.

Bright chemiluminescent dioxetane probes for the detection of gaseous transmitter H2S.

Hydrogen sulfide (H2S), the third gaseous transmitter after CO and NO, is a double-edged sword in the human body. A specific concentration of H2S can attenuate myocardial ischemia-reperfusion injury by preserving mitochondrial function, in contrast, cause illness, including inflammation and stroke. There are already some probes for the real-time monitoring of the level of H2S in the biological environment. However, they have some disadvantages, such as phototoxicity, low sensitivity, and low quantum yield. In this research, by linking 4-dinitrophenyl-ether (DNP), a specific recognition group for H2S, with a chemiluminophore 1,2-dioxetane, we designed and synthesized the probe SCL-1. To tackle the barrier that the traditional chemiluminescent group has a short emission wavelength and is not easy to penetrate deep tissues, an acrylonitrile electron-withdrawing substituent was installed to the ortho-position of the 1,2-dioxanol hydroxy group. According to the same design strategy as SCL-1, the probe SCL-2 was designed with the modified chemiluminescent group. Studies have shown that SCL-2 with electron-withdrawing acrylonitrile has higher luminescence quantum yield and high sensitivity than SCL-1, realizing real-time detection of H2S in vitro and in vivo. The LOD of SCL-2 was 0.185 µM, which was the best among the currently available luminescent probes for detecting H2S. We envisage that SCL-2 may be a practical toolbox for studying the biological functions of H2S and H2S-related diseases.

Post-Traumatic Growth Experiences among COVID-19 Confirmed Cases in China: A Qualitative Study.

COVID-19 infection can cause psychological distress and profoundly impact patients' lives, but it can also lead to positive changes and post-traumatic growth (PTG), or positive psychological change in response to challenging life circumstances. Current research on the influence of COVID-19 infection has mainly focused on its negative effects. Therefore, the aim of this study was to investigate whether patients with COVID-19 in China experienced PTG and, if so, what changed for them during the process of PTG. We used a qualitative descriptive approach to conduct this study. Using the purposive sampling recruitment method, patients with a confirmed COVID-19 diagnosis were recruited from a COVID-19 designated hospital in Shanghai, China, from April to July 2020. Data were collected using semi-structured, in-depth interviews conducted via cell phone or in person while social distancing to prevent the spread of COVID-19. Forty confirmed COVID-19 patients (19-68 years old) were recruited. Several prominent themes and subthemes were extracted from the interview responses regarding participants' experiences of PTG. The following are among the positive changesthat occurred for these participants after their diagnosis of COVID-19: (1) Reevaluation of their life priorities, which included a greater appreciation of being alive and re-evaluating their values and goals, (2) Improved relationships within their social circles, which included establishing or maintaining closer relationships with family and friends and a greater willingness to help others, and (3) Perceived changes regarding themselves, which included personal growth and increased awareness of the importance of their health. The study identified potential positive impacts of COVID-19 on patients, which could be helpful in the implementation of interventions to facilitate PTG among COVID-19 survivors.

Disclosure experience among COVID-19-confirmed patients in China: A qualitative study.

AIM: To understand COVID patients' experiences of and perspectives on disclosure of their illness and to explore and describe the factors affecting disclosure decisions among COVID patients in China. BACKGROUND: Disease disclosure is a critical component of prevention and control of a virus outbreak, and this is especially true during the COVID-19 pandemic. Understanding COVID patients' experiences and perspectives on disclosure could play a vital role in COVID management. DESIGN: A qualitative study. METHODS: A semi-structured interview guide was used to conduct qualitative in-depth interviews from April to June 2020. All the interviews were audio-recorded and transcribed, and then, a thematic analysis was conducted. The Standards for Reporting Qualitative Research (SRQR) were applied to this study. RESULTS: A total of 26 COVID-confirmed patients were recruited for the in-depth interviews. Four themes emerged from the thematic analysis on disclosure: persons disclosed to, reasons for disclosure, reasons for nondisclosure and impact of disclosure. The participants disclosed their COVID diagnosis to different groups, including family, close friends, community members and workplace contacts. The main reasons for disclosure included the following: government policy, social responsibility, gaining support and fear of being blamed for nondisclosure. However, some participants decided not to disclose to some groups for fear of facing stigma and discrimination or to protect family members from discrimination. Despite the potential benefits of obtaining support after disclosure, many participants did experience stigma and discrimination, privacy exposure, psychological distress and social isolation. CONCLUSIONS: An individual's decision as to whether to disclose their COVID-positive status is affected by many factors. To prevent the spread of COVID-19 and reduce the potential risks of disclosure, such as discrimination and privacy exposure, a balanced intervention should be designed to protect COVID patients and to secure any contact tracing. Therefore, the chances of discrimination could be decreased and patients' confidentiality could be protected. RELEVANCE TO CLINICAL PRACTICE: As the number of COVID patients increases, disclosure of an individual's infectious status is encouraged by health departments. Despite the potential benefits of disclosure, discrimination and privacy exposure should not be ignored. A disclosure protocol is necessary to ensure patients' privacy regarding their COVID status.

[Pd(NHC)(µ-Cl)Cl]2: Versatile and Highly Reactive Complexes for Cross-Coupling Reactions that Avoid Formation of Inactive Pd(I) Off-Cycle Products.

The development of more reactive, general, easily accessible, and readily available Pd(II)-NHC precatalysts remains a key challenge in homogeneous catalysis. In this study, we establish air-stable NHC-Pd(II) chloro-dimers, [Pd(NHC)(µ-Cl)Cl]2, as the most reactive Pd(II)-NHC catalysts developed to date. Most crucially, compared with [Pd(NHC)(allyl)Cl] complexes, replacement of the allyl throw-away ligand with chloride allows for a more facile activation step, while effectively preventing the formation of off-cycle [Pd2(µ-allyl)(µ-Cl)(NHC)2] products. The utility is demonstrated via broad compatibility with amide cross-coupling, Suzuki cross-coupling, and the direct, late-stage functionalization of pharmaceuticals. Computational studies provide key insight into the NHC-Pd(II) chloro-dimer activation pathway. A facile synthesis of NHC-Pd(II) chloro-dimers in one-pot from NHC salts is reported. Considering the tremendous utility of Pd-catalyzed cross-coupling reactions and the overwhelming success of [Pd(NHC)(allyl)Cl] precatalysts, we believe that NHC-Pd(II) chloro-dimers, [Pd(NHC)(µ-Cl)Cl]2, should be considered as go-to precatalysts of choice in cross-coupling processes.

Discovery of Small-Molecule Sulfonamide Fluorescent Probes for GPR120.

GPR120 is a novel target for the treatment of metabolic disease and type 2 diabetes. The small-molecule fluorescent probe could help us locate GPR120 visually and guide in-depth study of GPR120. In this study, we synthesized six nonacidic sulfonamide fluorescent probes and tested their optical and biological properties. Compared to previous probes for GPR120, these probes, with sulfonamide structure, have high selectivity on GPR120. We used these probes to establish a BRET binding assay system to screen agonists and antagonists of GPR120. It is expected that these novel fluorescent probes may become useful tools in studying pharmacology and physiology of GPR120.