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1.
Chemistry ; 30(11): e202303883, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38085637

RESUMO

We report a rapid, efficient, and scope-extensive approach for the late-stage electrochemical diselenation of BODIPYs. Photophysical analyses reveal red-shifted absorption - corroborated by TD-DFT and DLPNO-STEOM-CCSD computations - and color-tunable emission with large Stokes shifts in the selenium-containing derivatives compared to their precursors. In addition, due to the presence of the heavy Se atoms, competitive ISC generates triplet states which sensitize 1 O2 and display phosphorescence in PMMA films at RT and in a frozen glass matrix at 77 K. Importantly, the selenium-containing BODIPYs demonstrate the ability to selectively stain lipid droplets, exhibiting distinct fluorescence in both green and red channels. This work highlights the potential of electrochemistry as an efficient method for synthesizing unique emission-tunable fluorophores with broad-ranging applications in bioimaging and related fields.


Assuntos
Selênio , Estrutura Molecular , Compostos de Boro , Fluorescência , Corantes Fluorescentes
2.
Chemistry ; 30(11): e202400244, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38299452

RESUMO

Invited for the cover of this issue are the groups of Holger Braunschweig at the Julius-Maximilians-Universität Würzburg, Germany and Eufrânio N. da Silva Júnior at the Universidade Federal de Minas Gerais, UFMG, Brazil. The image depicts the electrochemical synthesis of selenium-containing BODIPY molecules with lightning symbolizing the electrifying synthetic process, while the surrounding elemental chaos hints at the red-shifted absorption and emission and the transformative photophysical properties of these new compounds. Read the full text of the article at 10.1002/chem.202303883.

3.
Chem Soc Rev ; 52(18): 6359-6378, 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37655711

RESUMO

Transition-metal catalyzed C-H activation reactions have been proven to be useful methodologies for the assembly of synthetically meaningful molecules. This approach bears intrinsic peculiarities that are important to be studied and comprehended in order to achieve its best performance. One example is the use of additives for the in situ generation of catalytically active species. This strategy varies according to the type of additive and the nature of the pre-catalyst that is being used. Thus, silver(I)-salts have proven to play an important role, due to the resulting high reactivity derived from the pre-catalysts of the main transition metals used so far. While being powerful and versatile, the use of silver-based additives can raise concerns, since superstoichiometric amounts of silver(I)-salts are typically required. Therefore, it is crucial to first understand the role of silver(I) salts as additives, in order to wisely overcome this barrier and shift towards silver-free systems.

4.
Angew Chem Int Ed Engl ; 63(18): e202400188, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38445547

RESUMO

The first systematic exploration of the synthesis and reactivity of naphthoquinonynes is described. Routes to two regioisomeric Kobayashi-type naphthoquinonyne precursors have been developed, and the reactivity of the ensuing 6,7- and 5,6-aryne intermediates has been investigated. Remarkably, these studies have revealed that a broad range of cycloadditions, nucleophile additions and difunctionalizations can be achieved while maintaining the integrity of the highly sensitive quinone unit. The methodologies offer a powerful diversity oriented approach to C6 and C7 functionalized naphthoquinones, which are typically challenging to access. From a reactivity viewpoint, the study is significant because it demonstrates that aryne-based functionalizations can be utilized strategically in the presence of highly reactive and directly competing functionality.

5.
Angew Chem Int Ed Engl ; 63(21): e202402777, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38501403

RESUMO

Diboradiazene compounds, derived in one step from the boron-mediated reduction of dinitrogen (N2), were treated separately with sulfur and acetic anhydride, providing heterocyclic compounds that are BN isosteres of thiophene and 1,3-oxazole, respectively. These simple reactions represent the final steps in two-step routes to complex heterocycles from N2 that both circumvent the need for transition metal reagents and completely bypass the traditional intermediate ammonia.

6.
Chem Res Toxicol ; 36(1): 66-82, 2023 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-36548215

RESUMO

Cancer incidence is increasing, and the drugs are not very selective. These drugs cause adverse effects, and the cells become resistant. Therefore, new drugs are needed. Here, we evaluated the effects of ZIM, a candidate for chemotherapy, and 4-AA alone and in association with commercial chemotherapeutic agents. Subsequently, the results of ZIM and 4-AA were compared. Male Swiss mice were treated with doses of 12, 24, or 48 mg/kg ZIM or 4-AA alone or in association with cisplatin (6 mg/kg), doxorubicin (16 mg/kg), and cyclophosphamide (100 mg/kg). Biometric parameters, DNA damage (comet and micronuclei), cell death, and splenic phagocytosis were evaluated. DNA docking was also performed to confirm the possible interactions of ZIM and 4-AA with DNA. 4-AA has been shown to have low genotoxic potential, increase the frequency of cell death, and activate phagocytosis. ZIM causes genomic and chromosomal damage in addition to causing cell death and activating phagocytosis. In association with chemotherapeutical agents, both 4-AA and ZIM have a chemopreventive effect and, therefore, reduce the frequency of DNA damage, cell death, and splenic phagocytosis. The association of 4-AA and ZIM with commercial chemotherapeutic agents increased the frequency of lymphocytes compared to chemotherapeutic agents alone. Molecular docking demonstrated that ZIM has more affinity for DNA than 4-AA and its precursors (1 and 2). This was confirmed by the lower interaction energy of the complex (-119.83 kcal/mol). ZIM can break the DNA molecule and, therefore, its chemotherapeutic effect can be related to DNA damage. It is considered that ZIM has chemotherapeutic potential. However, it should not be used in combination with cisplatin, doxorubicin, and cyclophosphamide as it reduces the effects of these drugs.


Assuntos
Antineoplásicos , Cisplatino , Camundongos , Animais , Masculino , Cisplatino/toxicidade , Ampirona/farmacologia , Simulação de Acoplamento Molecular , Morte Celular , Ciclofosfamida/farmacologia , Doxorrubicina/farmacologia , Dano ao DNA , DNA , Norbornanos/farmacologia , Antineoplásicos/toxicidade
7.
Org Biomol Chem ; 21(22): 4606-4619, 2023 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-37042164

RESUMO

In this work, we describe the design, synthesis, characterization, photophysical evaluation, DFT calculations, and application of two novel fluorescent benzothiadiazole (BTD) sensors for hydrazine detection and quantification at the cellular and multicellular (in vivo) levels. The two probes were fully characterized, and their photophysical properties were evaluated. We tested the designed fluorogenic dye (named BTD-CHO) as a selective sensor for the rapid, sensitive, and selective detection of hydrazine. When treated with N2H4, the probe affords a new derivative named BTD-HZN, releasing water as the only byproduct. BTD-CHO exhibited a preference for lipid droplets (LDs) and accumulated inside these organelles. Hydrazine detection in LDs could be carried out by the in situ formation of BTD-HZN inside live cells. We efficiently visualized the lipids of a challenging cellular model, microalgae (Chlorella sorokiniana), using these sensors. In vivo experiments indicated rapid and efficient detection of the analyte using C. elegans and zebrafish (Danio rerio) as the multicellular models.


Assuntos
Chlorella , Corantes Fluorescentes , Animais , Gotículas Lipídicas , Peixe-Zebra , Caenorhabditis elegans , Hidrazinas
8.
Bioorg Med Chem ; 94: 117479, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37769443

RESUMO

Chronic diseases such as cystic fibrosis, inflammatory bowel diseases, rheumatoid arthritis, and cardiovascular illness have been linked to a decrease in selenium levels and an increase in oxidative stress. Selenium is an essential trace element that exhibits antioxidant properties, with selenocysteine enzymes like glutathione peroxidase being particularly effective at reducing peroxides. In this study, a series of synthetic organoselenium compounds were synthesized and evaluated for their potential antioxidant activities. The new selenohydantoin molecules were inspired by selenoneine and synthesized using straightforward methods. Their antioxidant potential was evaluated and proven using classical radical scavenging and metal-reducing methods. The selenohydantoin derivatives exhibited glutathione peroxidase-like activity, reducing hydroperoxides. Theoretical calculations using Density Functional Theory (DFT) revealed the selenone isomer to be the only one occurring in solution, with selenolate as a possible tautomeric form in the presence of a basic species. Cytocompatibility assays indicated that the selenohydantoin derivatives were non-toxic to primary human aortic smooth muscle cells, paving the way for further biological evaluations of their antioxidant activity. The results suggest that selenohydantoin derivatives with trifluoro-methyl (-CF3) and chlorine (-Cl) substituents have significant activities and could be potential candidates for further biological trials. These compounds may contribute to the development of effective therapies for chronic diseases such cardiovascular diseases.

9.
Molecules ; 28(5)2023 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-36903471

RESUMO

In 2021, our research group published the prominent anticancer activity achieved through the successful combination of two redox centres (ortho-quinone/para-quinone or quinone/selenium-containing triazole) through a copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The combination of two naphthoquinoidal substrates towards a synergetic product was indicated, but not fully explored. Herein, we report the synthesis of 15 new quinone-based derivatives prepared from click chemistry reactions and their subsequent evaluation against nine cancer cell lines and the murine fibroblast line L929. Our strategy was based on the modification of the A-ring of para-naphthoquinones and subsequent conjugation with different ortho-quinoidal moieties. As anticipated, our study identified several compounds with IC50 values below 0.5 µM in tumour cell lines. Some of the compounds described here also exhibited an excellent selectivity index and low cytotoxicity on L929, the control cell line. The antitumour evaluation of the compounds separately and in their conjugated form proved that the activity is strongly enhanced in the derivatives containing two redox centres. Thus, our study confirms the efficiency of using A-ring functionalized para-quinones coupled with ortho-quinones to obtain a diverse range of two redox centre compounds with potential applications against cancer cell lines. Here as well, it literally takes two for an efficient tango!


Assuntos
Naftoquinonas , Quinonas , Animais , Camundongos , Quinonas/química , Benzoquinonas , Naftoquinonas/química , Oxirredução , Química Click , Reação de Cicloadição
10.
J Chem Inf Model ; 62(24): 6553-6573, 2022 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-35960688

RESUMO

The worldwide COVID-19 pandemic caused by the coronavirus SARS-CoV-2 urgently demands novel direct antiviral treatments. The main protease (Mpro) and papain-like protease (PLpro) are attractive drug targets among coronaviruses due to their essential role in processing the polyproteins translated from the viral RNA. In this study, we virtually screened 688 naphthoquinoidal compounds and derivatives against Mpro of SARS-CoV-2. Twenty-four derivatives were selected and evaluated in biochemical assays against Mpro using a novel fluorogenic substrate. In parallel, these compounds were also assayed with SARS-CoV-2 PLpro. Four compounds inhibited Mpro with half-maximal inhibitory concentration (IC50) values between 0.41 µM and 9.0 µM. In addition, three compounds inhibited PLpro with IC50 ranging from 1.9 µM to 3.3 µM. To verify the specificity of Mpro and PLpro inhibitors, our experiments included an assessment of common causes of false positives such as aggregation, high compound fluorescence, and inhibition by enzyme oxidation. Altogether, we confirmed novel classes of specific Mpro and PLpro inhibitors. Molecular dynamics simulations suggest stable binding modes for Mpro inhibitors with frequent interactions with residues in the S1 and S2 pockets of the active site. For two PLpro inhibitors, interactions occur in the S3 and S4 pockets. In summary, our structure-based computational and biochemical approach identified novel naphthoquinonal scaffolds that can be further explored as SARS-CoV-2 antivirals.


Assuntos
Antivirais , Proteases 3C de Coronavírus , Proteases Semelhantes à Papaína de Coronavírus , Naftoquinonas , Inibidores de Proteases , SARS-CoV-2 , Humanos , Antivirais/farmacologia , Antivirais/química , COVID-19 , Simulação de Acoplamento Molecular , Naftoquinonas/química , Naftoquinonas/farmacologia , Papaína , Inibidores de Proteases/farmacologia , Inibidores de Proteases/química , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/enzimologia , Proteases 3C de Coronavírus/antagonistas & inibidores , Proteases Semelhantes à Papaína de Coronavírus/antagonistas & inibidores
11.
J Fluoresc ; 32(4): 1299-1308, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35362933

RESUMO

Dropcast films produced from blends solutions of phenazine 1,2,3-triazole molecules in very low concentrations in a 1,3-Bis (N-carbazolyl) benzene (mCP) matrix were investigated at room tem-perature. The mCP acts as an optically inert matrix, having no influence on the emission properties of the guest molecules. Its conductive properties ensure the blend films as completely organic active layers. The fluorescent and phosphorescent emissions of the guest molecules in blue, green, red and also in white are relatively intense, without the need to mix different organic materials. The excitation of the system occurs directly by the incident laser beam on the films. The steady-state spectroscopy for the blue monomer and green dimer singlet fluorescence emissions were investigated. The analysis of their temporal decays was done using a different approach based on the Exponentially Modified Gaussian function. The phosphorescent emissions of the triplet steady-states, in the orange or in the red wavelength regions, were observed to be correlated, respectively, to the formation of guest monomers or to the guest dimers singlet states.

12.
Phys Chem Chem Phys ; 24(2): 1183-1190, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34931633

RESUMO

This work reports a classification analysis method based on the vibrational Raman spectra of 38 quinones and related structures, spectrally ordering and classifying the compounds. The molecular systems are relevant for chemical and biological processes, with applications in pharmacology, toxicology and medicine. The classification strategy uses a combination of principal component analysis with K-means clustering methods. Both theoretical simulations and experimental data are analysed, thus establishing their spectral characteristics, as related to their chemical structures and properties. The protocol introduced here should be broadly applicable in other molecular and solid state systems.

13.
Bioorg Chem ; 124: 105754, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35469631

RESUMO

Inflammation is a natural response of the organism to an infection, trauma, or cellular stress. Pain is the first symptom of acute and chronic inflammation. The standard class of medication to treat inflammatory pain is the nonsteroidal anti-inflammatory drug (NSAID). These drugs are associated with severe side effects such as gastric ulcers, gastritis, or internal bleeding. One of NSAIDs, Dipyrone® (metamizole) is largely used in many European and South American countries despite its dubious effectivity and its withdrawal from the market of several countries. Here, aiming to identify a new anti-inflammatory drug prototype based on Dipyrone® structure, a set of 27 molecules were virtually screened, and 4 compounds containing the active metabolite 4-aminoantipyrine and 1,4-dioxo-2-butenyl fragment were selected for docking, synthesis, and biological evaluation. The selection was based on the number of H-bonds and π- π stacking interactions between the inhibitor and the amino acids within the binding site of the enzyme. Carrageenan-induced paw edema, acetic acid-induced writhing, and formalin assays were used to evaluate inflammation and pain response. The selected compounds 1-4 inhibited the involvement of biogenic amines in the formation of paw edema. Compounds 1-4 also reduced pain in the inflammatory response phase. It has to be noted that 4-AA may cause agranulocytosis, which should be borne in mind when developing drug candidates of similar structure. Our new drug prototypes based on 4-aminoantipyrine and 1,4-dioxo-2-butenyl moieties open a gate for developing a prototype of nonsteroidal anti-inflammatory drugs.


Assuntos
Ampirona , Dipirona , Aminas/uso terapêutico , Analgésicos/química , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Carragenina , Dipirona/efeitos adversos , Edema/induzido quimicamente , Edema/tratamento farmacológico , Humanos , Inflamação/tratamento farmacológico , Dor/induzido quimicamente , Dor/tratamento farmacológico
14.
Chemistry ; 27(49): 12453-12508, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34038596

RESUMO

Synthetic organic chemistry has witnessed a plethora of functionalization and defunctionalization strategies. In this regard, C-H functionalization has been at the forefront due to the multifarious applications in the development of simple to complex molecular architectures and holds a brilliant prospect in drug development and discovery. Despite been explored tremendously by chemists, this functionalization strategy still enjoys the employment of novel metal catalysts as well metal-free organic ligands. Moreover, the switch to photo- and electrochemistry has widened our understanding of the alternative pathways via which a reaction can proceed and these strategies have garnered prominence when applied to C-H activation. Synthetic chemists have been foraging for new directing groups and templates for the selective activation of C-H bonds from a myriad of carbon-hydrogen bonds in aromatic as well as aliphatic systems. As a matter of fact, by varying the templates and directing groups, scientists found the answer to the challenge of distal C-H bond activation which remained an obstacle for a very long time. These templates have been frequently harnessed for selectively activating C-H bonds of natural products, drugs, and macromolecules decorated with multiple C-H bonds. This itself was a challenge before the commencement of this field as functionalization of a site other than the targeted site could modify and hamper the biological activity of the pharmacophore. Total synthesis and pharmacophore development often faces the difficulty of superfluous reaction steps towards selective functionalization. This obstacle has been solved by late-stage functionalization simply by harnessing C-H bond activation. Moreover, green chemistry and metal-free reaction conditions have seen light in the past few decades due to the rising concern about environmental issues. Therefore, metal-free catalysts or the usage of non-toxic metals have been recently showcased in a number of elegant works. Also, research groups across the world are developing rational strategies for directing group free or non-directed protocols that are just guided by ligands. This review encapsulates the research works pertinent to C-H bond activation and discusses the science devoted to it at the fundamental level. This review gives the readers a broad understanding of how these strategies work, the execution of various metal catalysts, and directing groups. This not only helps a budding scientist towards the commencement of his/her research but also helps a matured mind searching out for selective functionalization. A detailed picture of this field and its progress with time has been portrayed in lucid scientific language with a motive to inculcate and educate scientific minds about this beautiful strategy with an overview of the most relevant and significant works of this era. The unique trait of this review is the detailed description and classification of various directing groups and their utility over a wide substrate scope. This allows an experimental chemist to understand the applicability of this domain and employ it over any targeted substrate.


Assuntos
Carbono , Metais , Catálise , Feminino , Humanos , Ligação de Hidrogênio , Ligantes , Masculino
15.
Chem Rec ; 21(10): 2602-2603, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34633726

RESUMO

The 18th Brazilian Meeting on Organic Synthesis (18th BMOS) was planned to be held in Tiradentes, Brazil from October 2020. Due to the pandemic caused by the new coronavirus, the event was initially postponed until 2021 and will finally take place in late 2022. This Special Collection of The Chemical Record is organized together with Guest Editors Ângelo de Fátima and Eufrânio N. da Silva Júnior from Federal University of Minas Gerais and features contributions by present and previous participants of the conferene in the field of Organic Synthesis.

16.
Chem Rec ; 21(10): 2604-2637, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33415843

RESUMO

Metal-catalysed C-H functionalization has emerged as a powerful platform for the derivatization of quinones, a class of compounds with wide-ranging applications. This review organises and discusses the evolution of this chemistry from early Fujiwara-Moritani reactions, through to modern directing-group assisted C-H functionalization processes, including C-H functionalization reactions directed by the quinone ring itself. Mechanistic details of these reactions are provided to afford insight into how the unique reactivity of quinoidal compounds has been leveraged in each example.

17.
Chem Rec ; 21(10): 2702-2738, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34170622

RESUMO

Diverse structural frameworks are found in natural compounds and are well known for their chemical and biological properties; such compounds include the imidazoles and oxazoles. Researchers worldwide are continually working on the development of methods for synthesizing new molecules bearing these basic moiety and evaluating their properties and applications. To expand the knowledge related to azoles, this review summarizes important examples of imidazole and oxazole derivatives from 1,2-dicarbonyl compounds, such as lapachones and phenanthrene-9,10-diones, not only regarding their synthesis and biological applications but also their photophysical properties and uses. The data concerning the latter are particularly scarce in the literature, which leads to underestimation of the potential applications that can be envisaged for these compounds.


Assuntos
Oxazóis , Fenantrenos , Imidazóis
18.
J Org Chem ; 86(1): 264-278, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33306394

RESUMO

Rhodium(III) catalysis enabled C-H/N-H alkyne annulation of nonsymmetric imidazole derivatives. This study encompasses the synthesis of imidazoles from a naturally occurring quinoidal compound and their use for the preparation of rigid π-extended imidazole derivatives with outstanding fluorescence. Our study also brings to light the photophysical aspects and the mechanism of the reaction studied via computational calculations. This method provided an efficient and versatile tool for the synthesis of fluorescent compounds with a wide range of chemical and biological applications.

19.
Org Biomol Chem ; 19(3): 525-547, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33393535

RESUMO

Over the past few decades, regioselective catalytic C-H functionalization has provided an attractive tool for unique retrosynthetic disconnections. The advancement of the directing group strategy in metal catalyzed synthetic transformation has contributed significantly to the incorporation of a wide range of functionalization reactions in both aromatic systems and aliphatic backbones. However, the extensive utilization of these methodologies depends on the ease of removal of the directing group to restore the free functional group. In this review, we have summarised the reported approaches for removing/modifying versatile directing groups.

20.
Bioorg Med Chem ; 40: 116164, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-34020276

RESUMO

A diversity-oriented synthesis of hydroxylated aryl-quinones via CH oxygenation reactions and their evaluation against Trypanosoma cruzi, the etiological agent of Chagas disease, was accomplished. With the use of ruthenium(II)- or palladium(II)-based catalysts, complementary regioselectivities were observed in the hydroxylation reactions and we have identified 9 compounds more potent than benznidazole (Bz) among these novel arylated and hydroxylated quinones. For instance, 5-hydroxy-2-[4-(trifluoromethyl)phenyl]-1,4-naphthoquinone (4h) with an IC50/24 h value of 22.8 µM is 4.5-fold more active than the state-of-the-art drug Bz. This article provides the first example of the application of CH activation for the position-selective hydroxylation of arylated quinones and the identification of these compounds as trypanocidal drug candidates.


Assuntos
Oxigênio/química , Paládio/química , Quinonas/farmacologia , Rutênio/química , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Catálise , Doença de Chagas/tratamento farmacológico , Relação Dose-Resposta a Droga , Camundongos , Estrutura Molecular , Testes de Sensibilidade Parasitária , Quinonas/síntese química , Quinonas/química , Relação Estrutura-Atividade , Tripanossomicidas/síntese química , Tripanossomicidas/química
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