Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.419
Filtrar
1.
Science ; 371(6536): 1313, 2021 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-33766876
2.
Chemistry ; 27(19): 6094-6099, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33577120

RESUMO

Bioorthogonal reactions are ideally suited to selectively modify proteins in complex environments, even in vivo. Kinetics and product stability of these reactions are crucial parameters to evaluate their usefulness for specific applications. Strain promoted inverse electron demand Diels-Alder cycloadditions (SPIEDAC) between tetrazines and strained alkenes or alkynes are particularly popular, as they allow ultrafast labeling inside cells. In combination with genetic code expansion (GCE)-a method that allows to incorporate noncanonical amino acids (ncAAs) site-specifically into proteins in vivo. These reactions enable residue-specific fluorophore attachment to proteins in living mammalian cells. Several SPIEDAC capable ncAAs have been presented and studied under diverse conditions, revealing different instabilities ranging from educt decomposition to product loss due to ß-elimination. To identify which compounds yield the best labeling inside living mammalian cells has frequently been difficult. In this study we present a) the synthesis of four new SPIEDAC reactive ncAAs that cannot undergo ß-elimination and b) a fluorescence flow cytometry based FRET-assay to measure reaction kinetics inside living cells. Our results, which at first sight can be seen conflicting with some other studies, capture GCE-specific experimental conditions, such as long-term exposure of the ring-strained ncAA to living cells, that are not taken into account in other assays.


Assuntos
Alquinos , Aminoácidos , Animais , Reação de Cicloadição , Corantes Fluorescentes , Proteínas
3.
Anal Chem ; 93(4): 2610-2618, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33470097

RESUMO

Mass-spectrometry-based chemoproteomics has enabled the rapid and proteome-wide discovery of functional and potentially 'druggable' hotspots in proteins. While numerous transformations are now available, chemoproteomic studies still rely overwhelmingly on copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) or 'click' chemistry. The absence of bio-orthogonal chemistries that are functionally equivalent and complementary to CuAAC for chemoproteomic applications has hindered the development of multiplexed chemoproteomic platforms capable of assaying multiple amino acid side chains in parallel. Here, we identify and optimize Suzuki-Miyaura cross-coupling conditions for activity-based protein profiling and mass-spectrometry-based chemoproteomics, including for target deconvolution and labeling site identification. Uniquely enabled by the observed orthogonality of palladium-catalyzed cross-coupling and CuAAC, we combine both reactions to achieve dual labeling. Multiplexed targeted deconvolution identified the protein targets of bifunctional cysteine- and lysine-reactive probes.


Assuntos
Alquinos/química , Azidas/química , Cobre/química , Reação de Cicloadição/métodos , Proteômica/métodos , Catálise , Química Click , Células HEK293 , Humanos , Estrutura Molecular
4.
J Mol Graph Model ; 102: 107763, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33069124

RESUMO

The molecular electronic density theory (MEDT) was invested to elucidate the chemo-, regio- and stereo-selectivity of the 1,3-dipolar cycloaddition between Diazomethane (DZM) and Psilostachyin (PSH). The DFT method at B3LYP/6-31 + G (d,p) level of theory was used. Reactivity indices, transition structures theory, IGM and ELF analysis were employed to reveal the mechanism of the reaction. The addition of DZM to PSH takes place through a one-step mechanism and an asynchronous transition states. Eight possible addition channels of reaction were investigated (addition of C (sp2) to Diazomethane at C4, C5, C6 or C7). The addition of C (sp2) at C5 leading to P1 product is the preferred channel. The addition of ether does not affect the chemo-, regio- and stereo-selectivity of the reaction. Analysis of transfer of charges along the IRC path associated with the P1 product shows a polar character for the studied reaction. We have also used the noncovalent interaction (NCI) which is very helpful to reveal the most favored addition channel of the reaction, by analyzing the weak interactions in different TSs. Finally, we investigate about the potential of inhibition of some pyrazoline compounds against COVID-19-Mpro by performing a molecular docking calculations.


Assuntos
Antivirais/química , Antivirais/farmacologia , Lactonas/química , Lactonas/farmacologia , /enzimologia , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Proteínas da Matriz Viral/química , Proteínas da Matriz Viral/efeitos dos fármacos , /tratamento farmacológico , Reação de Cicloadição , Diazometano/química , Humanos , Simulação de Acoplamento Molecular , Pandemias , Inibidores de Proteases/química , Inibidores de Proteases/farmacologia , Conformação Proteica , Pirazóis/química , Pirazóis/farmacologia , Eletricidade Estática
5.
J Med Chem ; 63(24): 15693-15708, 2020 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-33325700

RESUMO

Conjugation of pleuromutilin is an attractive strategy for the development of novel antibiotics and the fight against multiresistant bacteria as the class is associated with low rates of resistance and cross-resistance development. Herein, the preparation of 35 novel (+)-pleuromutilin conjugates is reported. Their design was based on a synthetically more efficient benzyl adaption of a potent lead but still relied on the Cu(I)-catalyzed alkyne-azide [3 + 2] cycloaddition for conjugation onto pleuromutilin. Their antibacterial activity was evaluated against the multiresistant Staphylococcus aureus strain USA300 for which they displayed moderate to excellent activity. Compound 35, bearing a para-benzyladenine substituent, proved particularly potent against USA300 and additional strains of MRSA and displayed as importantly no cytotoxicity in four mammalian cell lines. Structure-activity relationship analysis revealed that the purine 6-amino is essential for high potency, likely because of strong hydrogen bonding with the RNA backbone of C2469, as suggested by a molecular model based on the MM-GBSA approach.


Assuntos
Adenina/química , Antibacterianos/farmacologia , Diterpenos/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Compostos Policíclicos/química , Triazóis/química , Animais , Antibacterianos/química , Sítios de Ligação , Catálise , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cobre/química , Reação de Cicloadição , Cães , Humanos , Testes de Sensibilidade Microbiana , Simulação de Dinâmica Molecular , Relação Estrutura-Atividade
6.
Yakugaku Zasshi ; 140(10): 1213-1224, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32999200

RESUMO

In basic pharmaceutical sciences to achieve drug development, research on the efficient chemical synthesis of small molecules having cyclic skeletons is important. We have been engaged in the development of artificial catalysts for asymmetric ring formation reactions that exclusively synthesize right-handed or left-handed cyclic compounds and have achieved the construction of optically active cyclic skeletons using our original catalysts. The synthesis of biologically active compounds was facilitated through six-membered ring construction by Diels-Alder reaction of Danishefsky diene; however, no asymmetric variant of the reaction has been achieved. We approached this unresolved issue using multi-coordinated lanthanide metals. A new chiral lanthanide catalyst was developed, and the catalytic asymmetric Diels-Alder reaction of Danishefsky diene was realized for the first time. By modifying the chemical structure of Danishefsky diene, we applied the lanthanide catalyst to the syntheses of polycyclic compounds and biologically active compounds. We achieved the asymmetric synthesis of natural products, antibacterial and antimalarial compounds, and an anti-obesity drug lead compound. Moreover, the novel catalyst exhibited higher performance than the previously reported ones. The latest generation of the catalyst can be handled stably in air at room temperature. Furthermore, we succeeded in the development of new catalysts by focusing on the properties of its metal precursors, such as nickel and indium, and achieved the construction of polycyclic skeletons by using these catalysts.


Assuntos
Compostos Heterocíclicos/síntese química , Compostos Policíclicos/síntese química , Alcenos/química , Antibacterianos/síntese química , Fármacos Antiobesidade/síntese química , Antimaláricos/síntese química , Produtos Biológicos/síntese química , Catálise , Reação de Cicloadição , Desenvolvimento de Medicamentos , Índio , Elementos da Série dos Lantanídeos/química , Níquel , Estereoisomerismo
7.
Yakugaku Zasshi ; 140(10): 1225-1233, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32999201

RESUMO

This article describes our stereoselective and site-selective chemical methods for exploiting cationic heterocycles as electron-withdrawing groups (EWGs). We envisioned that the phosphoramide N-H proton of a pyridyl phosphoramide 3 would be activated by the cationic pyridinium moiety that is formed upon protonation. The resulting imide-like N-H proton and the acidic pyridinium proton of the pyridinium phosphoramide 3⋅HX cooperate together, making 3⋅HX a highly acidic dual Brønsted acid. The catalytic ability of 3⋅HX was demonstrated in the development of the first asymmetric Diels-Alder reaction between 1-amide dienes and maleimides. Focusing on the activation of N-bromosuccinimide (NBS) because of its structural similarity to maleimides, the enantioselective bromolactonization of trisubstituted olefinic acids was accomplished utilizing pyridyl phosphoramide 3f as a Brønsted base catalyst bearing an acidic N-H proton. Lastly, our strategy for the site-selective acylation of polyol compounds is described. In our system, a pyridine aldoxime ester 10, used as a mild acylating reagent, was activated by a catalytic amount of Lewis acid via the inductive effect of the cationic pyridinium moiety. The resulting metal complex preferentially attracted the alcohol with a Lewis basic site, thereby facilitating selective acylation via a template effect. This metal-template-driven strategy allowed for the site-selective acylation of diverse α-hydroxyamides, including unprotected N-glycolyl aminosugars.


Assuntos
Cátions/química , Cátions/síntese química , Química Orgânica/métodos , Desenvolvimento de Medicamentos/métodos , Elétrons , Compostos Heterocíclicos/química , Compostos Heterocíclicos/síntese química , Acilação , Amidas/química , Catálise , Complexos de Coordenação/química , Reação de Cicloadição , Ésteres/química , Compostos de Pralidoxima/química , Estereoisomerismo
8.
Phytochemistry ; 180: 112519, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33038551

RESUMO

The reaction mechanism of the intramolecular [2 + 2] cycloaddition from a jatrophane precursor to the gaditanane skeleton, an unprecedented 5/6/4/6-fused tetracyclic ring framework recently isolated from Euphorbia spp., was studied using the bond reactivity indices approach. Furthermore, six diterpenoids, including three undescribed jatrophanes isolated from E. gaditana Coss, were described. The structures of these compounds were deduced by a combination of 2D NMR spectroscopy and ECD data analysis.


Assuntos
Euphorbia , Reação de Cicloadição , Diterpenos , Estrutura Molecular
9.
Int J Nanomedicine ; 15: 7433-7450, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116480

RESUMO

Purpose: Salicyl (Sal) - among other oxygen functionalities - multi-walled carbon nanotubes (MWCNTs) and their nanohybrids are investigated as promising contrast agents (CA) in magnetic resonance imaging (MRI) or drug delivery platforms, due to their unique properties. The preliminary results and the literature reports were the motivation to endow high r2 relaxivities, excellent dispersibility in water, and biocompatibility to superparamagnetic MWCNTs nanohybrids. It was hypothesized that these goals could be achieved by, not described in the literature yet, two-stage oxygen functionalization of MWCNTs. Results: Two structurally different MWCNT materials differing in diameters (44 and 12 nm) and the iron content (4.7% and 0.5%) are studied toward the functionalization effect on the T2 relaxometric properties. MWCNT oxidation is typically the first step of functionalization resulting in "first generation" oxygen functional groups (OFGs) on the surface. Until now, the impact of OFGs on the relaxivity of MWCNT was not truly recognized, but this study sheds light on this issue. By follow-up functionalization of oxidized MWCNT with 4-azidosalicylic acid through [2+1] cycloaddition of the corresponding nitrene, "second generation" of oxygen functional groups is grafted onto the nanohybrid, ie, Sal functionality. Conclusion: The introduced OFGs are responsible for an almost 30% increase in the relaxivity, which leads to remarkable r2 relaxivity of 951 mM-1s-1 (419 (mg/mL)-1s-1), the unprecedented value reported to date for this class of CAs. Also, the resulting nanohybrids express low cytotoxicity and superb diffusion after subcutaneous injection to a mouse.


Assuntos
Meios de Contraste/química , Meios de Contraste/farmacologia , Imagem por Ressonância Magnética/métodos , Nanotubos de Carbono/química , Oxigênio/química , Animais , Azidas/química , Reação de Cicloadição , Camundongos Endogâmicos C57BL , Oxirredução , Prótons , Salicilatos/química , Água/química
10.
Nat Commun ; 11(1): 4193, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32826921

RESUMO

Photochemical reactions are a powerful tool in (bio)materials design due to the spatial and temporal control light can provide. To extend their applications in biological setting, the use of low-energy, long wavelength light with high penetration propertiesis required. Further regulation of the photochemical process by additional stimuli, such as pH, will open the door for construction of highly regulated systems in nanotechnology- and biology-driven applications. Here we report the green light induced [2+2] cycloaddition of a halochromic system based on a styrylquinoxaline moiety, which allows for its photo-reactivity to be switched on and off by adjusting the pH of the system. Critically, the [2+2] photocycloaddition can be activated by green light (λ up to 550 nm), which is the longest wavelength employed to date in catalyst-free photocycloadditions in solution. Importantly, the pH-dependence of the photo-reactivity was mapped by constant photon action plots. The action plots further indicate that the choice of solvent strongly impacts the system's photo-reactivity. Indeed, higher conversion and longer activation wavelengths were observed in water compared to acetonitrile under identical reaction conditions. The wider applicability of the system was demonstrated in the crosslinking of an 8-arm PEG to form hydrogels (ca. 1 cm in thickness) with a range of mechanical properties and pH responsiveness, highlighting the potential of the system in materials science.


Assuntos
Reação de Cicloadição/métodos , Hidrogéis/química , Luz , Processos Fotoquímicos , Animais , Catálise , Sobrevivência Celular , Fibroblastos , Concentração de Íons de Hidrogênio , Camundongos , Fótons , Polímeros/química , Reologia
11.
J Vis Exp ; (161)2020 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-32744529

RESUMO

The interest on nitrogen-containing heterocycles has expanded rapidly in the synthetic community since they are important motifs for new drugs. Traditionally, they were synthesized through thermal cycloaddition reactions, whereas today, photocatalysis is preferred due to the mild and efficient conditions. With this focus, a new photocatalytic method for the synthesis of nitrogen-containing heterocycles is highly desired. Here, we report a protocol for the biosynthesis of cercosporin, which could function as a metal-free photocatalyst. We then illustrate cercosporin-photocatalyzed protocols for the synthesis of nitrogen-containing heterocycles 1,2,3-thiadiazoles through annulation of azoalkenes with KSCN, and synthesis of 1,4,5,6-tetrahydropyridazines [4+2] through cyclodimerization of azoalkenes under mild conditions, respectively. As a result, there is a new bridge between the microbial fermentation method and organic synthesis in a mild, cost-effective, environmentally friendly and sustainable manner.


Assuntos
Alcenos/química , Compostos Azo/química , Perileno/análogos & derivados , Técnicas de Química Sintética , Reação de Cicloadição , Metais/química , Nitrogênio/química , Perileno/química
12.
Int J Nanomedicine ; 15: 3983-3999, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606660

RESUMO

Introduction: In recent years, the use of cost-effective, multifunctional, environmentally friendly and simple prepared nanomaterials/nanoparticles have been emerged considerably. In this manner, different synthesizing methods were reported and optimized, but there is still lack of a comprehensive method with multifunctional properties. Materials and Methods: In this study, we aim to synthesis the copper oxide nanoparticles using Achillea millefolium leaf extracts for the first time. Catalytic activity was investigated by in situ azide alkyne cycloaddition click and also A3 coupling reaction, and optimized in terms of temperature, solvent, and time of the reaction. Furthermore, the photocatalytic activity of the synthesized nanoparticles was screened in terms of degradation methylene blue dye. Biological activity of the synthesized nanoparticles was evaluated in terms of antibacterial and anti-fungal assessments against Staphylococcus aureus, M. tuberculosis, E. coli, K. pneumoniae, P. mirabili, C. diphtheriae and S. pyogenes bacteria's and G. albicans, A. flavus, M. canis and G. glabrata fungus. In the next step, the biosynthesized CuO-NPs were screened by MTT and NTU assays. Results: Based on our knowledge, this is a comprehensive study on the catalytic and biological activity of copper oxide nanoparticles synthesizing from Achillea millefolium, which presents great and significant results (in both catalytic and biological activities) based on a simple and green procedure. Conclusion: Comprehensive biomedical and catalytic investigation of the biosynthesized CuO-NPs showed the mentioned method leads to synthesis of more eco-friendly nanoparticles. The in vitro studies showed promising and considerable results, and due to the great stability of these nanoparticles in a green media, effective biological activity considered as an advantageous.


Assuntos
Tecnologia Biomédica , Cobre/farmacologia , Nanopartículas Metálicas/química , Achillea/química , Antibacterianos/síntese química , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Bactérias/efeitos dos fármacos , Catálise , Sobrevivência Celular/efeitos dos fármacos , Reação de Cicloadição , Fungos/efeitos dos fármacos , Células Hep G2 , Humanos , Nanopartículas Metálicas/ultraestrutura , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Solventes/química , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , Fatores de Tempo , Difração de Raios X
13.
Nucleic Acids Res ; 48(13): 7356-7370, 2020 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-32520335

RESUMO

To enable the optimal, biocompatible and non-destructive application of the highly useful copper (Cu+)-mediated alkyne-azide 'click' cycloaddition in water, we have isolated and characterized a 79-nucleotide DNA enzyme or DNAzyme, 'CLICK-17', that harnesses as low as sub-micromolar Cu+; or, surprisingly, Cu2+ (without added reductants such as ascorbate) to catalyze conjugation between a variety of alkyne and azide substrates, including small molecules, proteins and nucleic acids. CLICK-17's Cu+ catalysis is orders of magnitude faster than that of either Cu+ alone or of Cu+ complexed to PERMUT-17, a sequence-permuted DNA isomer of CLICK-17. With the less toxic Cu2+, CLICK-17 attains rates comparable to Cu+, under conditions where both Cu2+ alone and Cu2+ complexed with a classic accelerating ligand, THPTA, are wholly inactive. Cyclic voltammetry shows that CLICK-17, unlike PERMUT-17, powerfully perturbs the Cu(II)/Cu(I) redox potential. CLICK-17 thus provides a unique, DNA-derived ligand environment for catalytic copper within its active site. As a bona fide Cu2+-driven enzyme, with potential for being evolved to accept only designated substrates, CLICK-17 and future variants promise the fast, safe, and substrate-specific catalysis of 'click' bioconjugations, potentially on the surfaces of living cells.


Assuntos
Cobre/metabolismo , Reação de Cicloadição/métodos , DNA Catalítico/química , Alquinos/química , Azidas/química , Química Click/métodos , Oxirredução , Água/química
14.
J Med Chem ; 63(13): 7392-7409, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32463228

RESUMO

Cancer cells rely on the enzyme telomerase (EC 2.7.7.49) to promote cellular immortality. Telomerase inhibitors (i.e., azidothymidine) can represent promising antitumor agents, although showing high toxicity when administered alone. Better outcomes were observed within a multipharmacological approach instead. In this context, we exploited the validated antitumor targets carbonic anhydrases (CAs; EC 4.2.1.1) IX and XII to attain the first proof of concept on CA-telomerase dual-hybrid inhibitors. Compounds 1b, 7b, 8b, and 11b showed good in vitro inhibition potency against the CAs IX and XII, with KI values in the low nanomolar range, and strong antitelomerase activity in PC-3 and HT-29 cells (IC50 values ranging from 5.2 to 9.1 µM). High-resolution X-ray crystallography on selected derivatives in the adduct with hCA II as a model study allowed to determine their binding modes and thus to set the structural determinants necessary for further development of compounds selectively targeting the tumoral cells.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Telomerase/antagonistas & inibidores , Zidovudina/química , Anidrase Carbônica II/antagonistas & inibidores , Anidrase Carbônica II/química , Anidrase Carbônica II/metabolismo , Inibidores da Anidrase Carbônica/química , Inibidores da Anidrase Carbônica/metabolismo , Inibidores da Anidrase Carbônica/farmacologia , Domínio Catalítico , Cristalografia por Raios X , Reação de Cicloadição , Desenho de Fármacos , Células HT29 , Humanos , Células PC-3 , Relação Estrutura-Atividade , Telomerase/genética , Telomerase/metabolismo , Triazóis/química
15.
Ecotoxicol Environ Saf ; 197: 110644, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32325330

RESUMO

Fludioxonil has been proven valuable as a broad-spectrum fungicide. However, there are concerns about its risk posed to non-target organisms in aquatic environments. In this paper, the mechanism, photoproducts transformation and eco-toxicity of fludioxonil during •OH/1O2-initiated process were systematically studied using quantum chemistry and computational toxicology. The results indicate that the two favorable pathways of •OH/1O2-initiated reactions are both occurred in pyrrole ring. It can conclude that the rate constants of •OH and 1O2 are 1.23 × 1010 and 3.69 × 107 M-1 s-1 at 298K, respectively, which results in half-lives of <2 days in surface waters under sunlit near-surface conditions. Based on toxicity assessments, these photoproducts showed a decreased aquatic toxicity but the majority products are still toxic. This study gives more insight into the chemical transformation mechanism of fludioxonil in aquatic environments.


Assuntos
Dioxóis/análise , Radical Hidroxila/química , Fotólise , Pirróis/análise , Oxigênio Singlete/química , Poluentes Químicos da Água/análise , Reação de Cicloadição , Dioxóis/química , Dioxóis/efeitos da radiação , Ecotoxicologia , Cinética , Pirróis/química , Pirróis/efeitos da radiação , Poluentes Químicos da Água/química , Poluentes Químicos da Água/efeitos da radiação
16.
Inorg Chem ; 59(7): 5231-5239, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32212684

RESUMO

With the aid of a pyridyl tetracarboxylate ligand, 2,5-bis(2',5'-dicarboxylphenyl)pyridine (H4L), two indium-organic frameworks, [In2(L)(OH)2]·2DMF·2H2O (1) and [Me2NH2][In(L)]·2.5NMF·4H2O (2), with (6,8)- and (4,4)-connected nets have been constructed in different solvent systems. Both 1 and 2 exhibit high thermal and chemical stability. Gas sorption behavior of 1 and 2 for N2, C2H2, C2H4, CO2, and CH4 indicate excellent separation selectivities of C2Hx/CH4 and CO2/CH4. Furthermore, 1 possesses a high density of Brønsted sites and shows efficient catalytic conversion for CO2 cycloaddition with epoxides. Meanwhile, luminescence investigations reveal that 2 can detect nitrofurazone efficiently.


Assuntos
Antibacterianos/análise , Dióxido de Carbono/química , Estruturas Metalorgânicas/química , Adsorção , Catálise , Reação de Cicloadição , Compostos de Epóxi/química , Índio/química , Ligantes , Porosidade , Piridinas/química , Espectrometria de Fluorescência
17.
Chem Commun (Camb) ; 56(29): 4078-4081, 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32159534

RESUMO

A novel method for the synthesis of 3-(2-quinolyl) chromones through a tandem [3+2] cycloaddition/ring-opening/O-arylation from ynones and quinoline N-oxides has been developed. This protocol proceeds under transition metal- and additive-free conditions and can be amplified to the gram level in 91% yield. 3-(1-Isoquinolyl) and 3-(2-pyridyl) chromones are also successfully synthesized using isoquinoline and pyridine N-oxides under basic conditions. Various heteroarene-contaning chromones were afforded in 30-98% yields, which are difficult to be obtained and are compounds of interest in pharmaceutical chemistry and chemical biology.


Assuntos
Cromonas/química , Óxidos/química , Quinolinas/química , Reação de Cicloadição
18.
Org Biomol Chem ; 18(12): 2252-2263, 2020 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-32149317

RESUMO

Glycoconjugates, due to their diverse functions, are widely regarded as biologically important molecules. Artemisinic acid 1 occurs naturally in the plant Artemisia annua and is considered to be the biogenetic precursor of the antimalarial drug, artemisinin 2. We report herein the design and synthesis of diverse artemisinic acid derived glycoconjugates. We have synthesized 12-O-artemisinic acid-glycoconjugates (7a-k) and 12-N-artemisinic acid-glycoconjugates (8a-k) by utilizing Cu(i)-catalyzed azide-alkyne cycloaddition reactions (Click chemistry) with various synthesized sugar azides (6a-k) in good to excellent yields along with two fluorescently labeled compounds, 12-O-artemisinic acid-glycoconjugate 11 and 12-N-artemisinic acid-glycoconjugate 12, to investigate the mode of action of these compounds in biological systems. All the synthesized artemisinic acid glycoconjugates were assayed for their efficacy against the MCF7 cell line. Our anticancer studies indicated that all the synthesized compounds inhibited the growth of MCF7 cells in a dose dependent manner, barring compounds 4 and 7d. However, these compounds exhibit moderate cytotoxicity, as is evident from their IC50 values.


Assuntos
Antineoplásicos/síntese química , Artemisininas/química , Glicoconjugados/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Azidas/química , Química Click , Reação de Cicloadição , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Glicoconjugados/farmacologia , Humanos , Concentração Inibidora 50 , Células MCF-7 , Sesquiterpenos/química
19.
Org Biomol Chem ; 18(11): 2051-2053, 2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-32141462

RESUMO

Total synthesis of isatindigotindoline C, a 3,3'-spiropyrrolidine oxindole alkaloid, is achieved in two steps using an exo-selective decarboxylative 1,3-dipolar cycloaddition as the key step. The synthesis verifies the originally assigned relative anti-stereochemistry for the bis-oxindole core of isatindigotindoline C.


Assuntos
Alcaloides Indólicos/síntese química , Reação de Cicloadição/métodos , Descarboxilação , Oxindois , Compostos de Espiro/síntese química
20.
J Vis Exp ; (157)2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-32176211

RESUMO

Fluorescent antibiotics are multipurpose research tools that are readily used for the study of antimicrobial resistance, due to their significant advantage over other methods. To prepare these probes, azide derivatives of antibiotics are synthesized, then coupled with alkyne-fluorophores using azide-alkyne dipolar cycloaddition by click chemistry. Following purification, the antibiotic activity of the fluorescent antibiotic is tested by minimum inhibitory concentration assessment. In order to study bacterial accumulation, either spectrophotometry or flow cytometry may be used, allowing for much simpler analysis than methods relying on radioactive antibiotic derivatives. Furthermore, confocal microscopy can be used to examine localization within the bacteria, affording valuable information about mode of action and changes that occur in resistant species. The use of fluorescent antibiotic probes in the study of antimicrobial resistance is a powerful method with much potential for future expansion.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Corantes Fluorescentes , Antibacterianos/química , Azidas/química , Bactérias/efeitos dos fármacos , Química Click , Reação de Cicloadição , Corantes Fluorescentes/química , Testes de Sensibilidade Microbiana , Microscopia Confocal
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...