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1.
Molecules ; 26(12)2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34201337

RESUMO

Addition of the silylated tag (STag) enables peptides to be highly soluble in CPME, allowing them to be used at high concentrations in a coupling reaction to enhance reactivity and achieve effective synthesis of sterically hindered peptides. We described the development of a continuous one-pot STag-assisted peptide synthesis platform as a method that provides near-stoichiometric, speedy, environmentally friendly, and scalable peptide synthesis.


Assuntos
Peptídeos/síntese química , Técnicas de Química Sintética/métodos , Éter/química , Química Verde/métodos
2.
Chimia (Aarau) ; 75(6): 480-483, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34233808

RESUMO

Flow chemistry has emerged as a powerful method for on-demand chemical synthesis and modification of peptides and proteins. Herein, we discuss the characteristics of flow chemistry and how they are applied to various aspects of peptide chemistry. We highlight recent advances in automated flow-based peptide synthesis, which extend the length of peptides routinely accessible to single-domain proteins and allow for the collection of time-resolved synthesis data. Applications of this data for the prediction of synthesis outcome and the potential for the development of more sustainable synthesis methods are also discussed. Finally, we will review solutionphase approaches, including flow-based ligation strategies and peptide cyclization. Throughout this review, the current challenges and potential future developments are highlighted.


Assuntos
Peptídeos , Proteínas , Técnicas de Química Sintética , Ciclização
3.
Chem Commun (Camb) ; 57(55): 6804-6807, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34236361

RESUMO

Glycosylation plays important roles in SARS-CoV-2 infection. We describe here a facile chemoenzymatic synthesis of core-fucosylated N-glycopeptides derived from the SARS-CoV-2 Spike protein and their binding with glycan-dependent neutralizing antibody S309 and human lectin CLEC4G. The synthetic glycopeptides provide tools for further functional characterization of viral glycosylation.


Assuntos
Glicopeptídeos/síntese química , Glicopeptídeos/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Anticorpos Neutralizantes/imunologia , Técnicas de Química Sintética , Glicopeptídeos/química , Glicopeptídeos/imunologia , Glicosilação , Polissacarídeos/metabolismo
4.
Int J Mol Sci ; 22(12)2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34208594

RESUMO

This article describes the synthesis and characterization of ß-cyclodextrin-based nano-sponges (NS) inclusion compounds (IC) with the anti-tumor drugs melphalan (MPH) and cytoxan (CYT), and the addition of gold nanoparticles (AuNPs) onto both systems, for the potential release of the drugs by means of laser irradiation. The NS-MPH and NS-CYT inclusion compounds were characterized using scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), energy dispersive spectroscopy (EDS), thermogravimetric analysis (TGA), UV-Vis, and proton nuclear magnetic resonance (1H-NMR). Thus, the inclusion of MPH and CYT inside the cavities of NSs was confirmed. The association of AuNPs with the ICs was confirmed by SEM, EDS, TEM, and UV-Vis. Drug release studies using NSs synthesized with different molar ratios of ß-cyclodextrin and diphenylcarbonate (1:4 and 1:8) demonstrated that the ability of NSs to entrap and release the drug molecules depends on the crosslinking between the cyclodextrin monomers. Finally, irradiation assays using a continuous laser of 532 nm showed that photothermal drug release of both MPH and CYT from the cavities of NSs via plasmonic heating of AuNPs is possible.


Assuntos
Ciclodextrinas , Ciclofosfamida/administração & dosagem , Portadores de Fármacos , Ouro , Melfalan/administração & dosagem , Nanopartículas Metálicas , Técnicas de Química Sintética , Ciclodextrinas/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos/efeitos da radiação , Ouro/química , Luz , Espectroscopia de Ressonância Magnética , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Temperatura , Termogravimetria , Tocoferóis , Difração de Raios X
5.
Int J Mol Sci ; 22(12)2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34204217

RESUMO

In this paper, the study of surface modification of two-dimensional (2D), non-luminescent CdS nanoplates (NPLs) by thiol-containing ligands is presented. We show that a process of twophase transfers with appropriate ligand exchange transforms non-luminescent NPLs into spherical CdS nanoparticles (NPs) exhibiting a blue photoluminescence with exceptionally high quantum yield ~90%. In the process, transfer from inorganic solvent to water is performed, with appropriately selected ligand molecules and pH values (forward phase transfer), which produces NPs with modified size and shape. Then, in reverse phase transfer, NPs are transferred back to toluene due to surface modification by combined Cd (OL)2 and Cd (Ac)2. As a result, spherical NPs are formed (average diameter between 4 and 6 nm) with PL QY as high as 90%. This is unique for core only CdS NPs without inorganic shell.


Assuntos
Compostos de Cádmio/química , Nanopartículas/química , Pontos Quânticos/química , Sulfetos/química , Fenômenos Químicos , Técnicas de Química Sintética , Nanopartículas/ultraestrutura , Transição de Fase , Análise Espectral
6.
Int J Mol Sci ; 22(12)2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34204295

RESUMO

Novel antiviral nanotherapeutics, which may inactivate the virus and block it from entering host cells, represent an important challenge to face viral global health emergencies around the world. Using a combination of bioorthogonal copper-catalyzed 1,3-dipolar alkyne/azide cycloaddition (CuAAC) and photoinitiated thiol-ene coupling, monofunctional and bifunctional peptidodendrimer conjugates were obtained. The conjugates are biocompatible and demonstrate no toxicity to cells at biologically relevant concentrations. Furthermore, the orthogonal addition of multiple copies of two different antiviral peptides on the surface of a single dendrimer allowed the resulting bioconjugates to inhibit Herpes simplex virus type 1 at both the early and the late stages of the infection process. The presented work builds on further improving this attractive design to obtain a new class of therapeutics.


Assuntos
Antivirais/farmacologia , Dendrímeros/farmacologia , Glicoproteínas , Herpesvirus Humano 1 , Peptídeos/farmacologia , Proteínas Virais , Sequência de Aminoácidos , Animais , Antivirais/química , Células CHO , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Fenômenos Químicos , Técnicas de Química Sintética , Cromatografia Líquida de Alta Pressão , Cricetulus , Dendrímeros/química , Glicoproteínas/química , Herpesvirus Humano 1/metabolismo , Testes de Sensibilidade Microbiana , Estrutura Molecular , Peptídeos/química , Análise Espectral , Proteínas Virais/química
7.
Nat Commun ; 12(1): 3389, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34099672

RESUMO

Bioorthogonal late-stage diversification of amino acids and peptides bears enormous potential for drug discovery and molecular imaging. Despite major accomplishments, these strategies largely rely on traditional, lengthy prefunctionalization methods, heavily involving precious transition-metal catalysis. Herein, we report on a resource-economical manganese(I)-catalyzed C-H fluorescent labeling of structurally complex peptides ensured by direct alkynylation and alkenylation manifolds. This modular strategy sets the stage for unraveling structure-activity relationships between structurally discrete fluorophores towards the rational design of BODIPY fluorogenic probes for real-time analysis of immune cell function.


Assuntos
Técnicas de Química Sintética/métodos , Corantes Fluorescentes/síntese química , Manganês/química , Peptídeos/síntese química , Compostos de Boro/química , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/metabolismo , Carbono/química , Catálise , Membrana Celular/metabolismo , Humanos , Hidrogênio/química , Células Jurkat , Microscopia Confocal , Microscopia de Fluorescência , Imagem Molecular/métodos
8.
Int J Mol Sci ; 22(9)2021 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-34065133

RESUMO

Low-molecular-weight organic ammonium salts exert excellent antimicrobial effects by interacting lethally with bacterial membranes. Unfortunately, short-term functionality and high toxicity limit their clinical application. On the contrary, the equivalent macromolecular ammonium salts, derived from the polymerization of monomeric ammonium salts, have demonstrated improved antibacterial potency, a lower tendency to develop resistance, higher stability, long-term activity, and reduced toxicity. A water-soluble non-quaternary copolymeric ammonium salt (P7) was herein synthetized by copolymerizing 2-methoxy-6-(4-vinylbenzyloxy)-benzylammonium hydrochloride monomer with N, N-di-methyl-acrylamide. The antibacterial activity of P7 was assessed against several multidrug-resistant (MDR) clinical isolates of both Gram-positive and Gram-negative species. Except for colistin-resistant Pseudomonas aeruginosa, most isolates were susceptible to P7, also including some Gram-negative bacteria with a modified charge in the external membrane. P7 showed remarkable antibacterial activity against isolates of Enterococcus, Staphylococcus, Acinetobacter, and Pseudomonas, and on different strains of Escherichia coli and Stenotrophomonas maltophylia, regardless of their antibiotic resistance. The lowest minimal inhibitory concentrations (MICs) observed were 0.6-1.2 µM and the minimal bactericidal concentrations (MBC) were frequently overlapping with the MICs. In 24-h time-kill and turbidimetric studies, P7 displayed a rapid non-lytic bactericidal activity. P7 could therefore represent a novel and potent tool capable of counteracting infections sustained by several bacteria that are resistant to the presently available antibiotics.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Compostos de Benzilamônio/química , Compostos de Benzilamônio/farmacologia , Polímeros , Antibacterianos/síntese química , Bactérias/efeitos dos fármacos , Compostos de Benzilamônio/síntese química , Técnicas de Química Sintética , Relação Dose-Resposta a Droga , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Polimerização , Polímeros/química , Análise Espectral
9.
Molecules ; 26(9)2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-34066468

RESUMO

NR+ is a highly effective vitamin B3 type supplement due to its unique ability to replenish NAD+ levels. While NR+ chloride is already on the market as a nutritional supplement, its synthesis is challenging, expensive, and low yielding, making it cumbersome for large-scale industrial production. Here we report the novel crystalline NR+ salts, d/l/dl-hydrogen tartrate and d/l/dl-hydrogen malate. Their high-yielding, one-pot manufacture does not require specific equipment and is suitable for multi-ton scale production. These new NR+ salts seem ideal for nutritional applications due to their bio-equivalence compared to the approved NR+ chloride. In addition, the crystal structures of all stereoisomers of NR+ hydrogen tartrate and NR+ hydrogen malate and a comparison to the known NR+ halogenides are presented.


Assuntos
Aditivos Alimentares/química , Tecnologia de Alimentos/métodos , Niacinamida/análogos & derivados , Niacinamida/química , Compostos de Piridínio/química , Ânions , Técnicas de Química Sintética , Cloretos , Cristalização , Suplementos Nutricionais , Hidrogênio/química , Espectroscopia de Ressonância Magnética , Malatos/química , Oxirredução , Sais , Estereoisomerismo , Tartaratos/química , Difração de Raios X
10.
Molecules ; 26(9)2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-34066575

RESUMO

Despite progress achieved, there is limited available information about the antibacterial activity of constituents of essential oils (EOs) from different medicinal-aromatic plants (MAPs) against fish pathogens and the complex interactions of blended EOs thereof. The present study aimed to investigate possible synergistic antimicrobial effects of EOs from seven Greek MAPs with strong potential against Aeromonas veronii bv. sobria, a fish pathogen associated with aquaculture disease outbreaks. The main objective was to evaluate whether blending of these EOs can lead to increased antimicrobial activity against the specific microorganism. A total of 127 combinations of EOs were prepared and their effect on A. veronii bv. sobria growth was tested in vitro. We examined both the inhibitory and bactericidal activities of the individual EOs and compared them to those of the blended EOs. The vast majority of the investigated combinations exhibited significant synergistic and additive effects, while antagonistic effects were evident only in a few cases, such as the mixtures containing EOs from rosemary, lemon balm and pennyroyal. The combination of EOs from Greek oregano and wild carrot, as well as the combinations of those two with Spanish oregano or savoury were the most promising ones. Overall, Greek oregano, savoury and Spanish oregano EOs were the most effective ones when applied either in pure form or blended with other EOs.


Assuntos
Aeromonas veronii/efeitos dos fármacos , Antibacterianos/farmacologia , Peixes/microbiologia , Infecções por Bactérias Gram-Negativas/prevenção & controle , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Animais , Apiaceae , Técnicas de Química Sintética , Daucus carota , Sinergismo Farmacológico , Cromatografia Gasosa-Espectrometria de Massas , Infecções por Bactérias Gram-Negativas/veterinária , Concentração Inibidora 50 , Melissa , Mentha , Testes de Sensibilidade Microbiana , Origanum , Plantas Medicinais/química , Rosmarinus , Satureja
11.
Molecules ; 26(9)2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-34066597

RESUMO

Thirty-three alkyl and aryl isothiocyanates, as well as isothiocyanate derivatives from esters of coded amino acids and from esters of unnatural amino acids (6-aminocaproic, 4-(aminomethyl)benzoic, and tranexamic acids), were synthesized with satisfactory or very good yields (25-97%). Synthesis was performed in a "one-pot", two-step procedure, in the presence of organic base (Et3N, DBU or NMM), and carbon disulfide via dithiocarbamates, with 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate (DMT/NMM/TsO-) as a desulfurization reagent. For the synthesis of aliphatic and aromatic isothiocyanates, reactions were carried out in a microwave reactor, and selected alkyl isothiocyanates were also synthesized in aqueous medium with high yields (72-96%). Isothiocyanate derivatives of L- and D-amino acid methyl esters were synthesized, under conditions without microwave radiation assistance, with low racemization (er 99 > 1), and their absolute configuration was confirmed by circular dichroism. Isothiocyanate derivatives of natural and unnatural amino acids were evaluated for antibacterial activity on E. coli and S. aureus bacterial strains, where the most active was ITC 9e.


Assuntos
Química Orgânica/métodos , Isotiocianatos/síntese química , Morfolinas/química , Tolueno/química , Triazinas/química , Aminas/química , Antibacterianos/química , Técnicas de Química Sintética , Cromatografia , Dicroísmo Circular , Escherichia coli/efeitos dos fármacos , Indicadores e Reagentes , Isotiocianatos/análise , Isotiocianatos/química , Espectroscopia de Ressonância Magnética , Micro-Ondas , Solventes , Staphylococcus aureus/efeitos dos fármacos , Enxofre/química , Temperatura
12.
Molecules ; 26(11)2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34067399

RESUMO

Pyrazolothiazole-substituted pyridine conjugates are an important class of heterocyclic compounds with an extensive variety of potential applications in the medicinal and pharmacological arenas. Therefore, herein, we describe an efficient and facile approach for the synthesis of novel pyrazolo-thiazolo-pyridine conjugate 4, via multicomponent condensation. The latter compound was utilized as a base for the synthesis of two series of 15 novel pyrazolothiazole-based pyridine conjugates (5-16). The newly synthesized compounds were fully characterized using several spectroscopic methods (IR, NMR and MS) and elemental analyses. The anti-proliferative impact of the new synthesized compounds 5-13 and 16 was in vitro appraised towards three human cancer cell lines: human cervix (HeLa), human lung (NCI-H460) and human prostate (PC-3). Our outcomes regarding the anti-proliferative activities disclosed that all the tested compounds exhibited cytotoxic potential towards all the tested cell lines with IC50 = 17.50-61.05 µM, especially the naphthyridine derivative 7, which exhibited the most cytotoxic potential towards the tested cell lines (IC50 = 14.62-17.50 µM) compared with the etoposide (IC50 = 13.34-17.15 µM). Moreover, an in silico docking simulation study was performed on the newly prepared compounds within topoisomerase II (3QX3), to suggest the binding mode of these compounds as anticancer candidates. The in silico docking results indicate that compound 7 was a promising lead anticancer compound which possesses high binding affinity toward topoisomerase II (3QX3) protein.


Assuntos
Técnicas de Química Sintética/métodos , Ensaios de Seleção de Medicamentos Antitumorais , Pirazóis/química , Piridinas/química , Tiazóis/química , Antineoplásicos/química , Linhagem Celular Tumoral , Simulação por Computador , DNA Topoisomerases Tipo II/química , Etoposídeo/farmacologia , Células HeLa , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Simulação de Acoplamento Molecular , Células PC-3 , Espectrofotometria Infravermelho
13.
Molecules ; 26(11)2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34067439

RESUMO

Ezetimibe is a well-known drug that lowers blood cholesterol levels by reducing its absorption in the small intestine when joining to Niemann-Pick C1-like protein (NPC1L1). A ligand-based study on ezetimibe analogues is reported, together with one-hit synthesis, highlighted in the study. A convenient asymmetric synthesis of (2S,3S)-N-α-(R)-methylbenzyl-3-methoxycarbonylethyl-4-methoxyphenyl ß-lactam is described starting from Baylis-Hillman adducts. The route involves a domino process: allylic acetate rearrangement, stereoselective Ireland-Claisen rearrangement and asymmetric Michael addition, which provides a δ-amino acid derivative with full stereochemical control. A subsequent inversion of ester and acid functionality paves the way to the lactam core after monodebenzylation and lactam formation. It also shows interesting results when it comes to a pharmacophore study based on ezetimibe as the main ligand in lowering blood cholesterol levels, revealing which substituents on the azetidine-2-one ring are more similar to the ezetimibe skeleton and will more likely bind to NPC1L1 than ezetimibe.


Assuntos
Técnicas de Química Sintética , Desenho de Fármacos , Ezetimiba/análogos & derivados , Ezetimiba/síntese química , Alelos , Amidas/química , Aminoácidos/química , Anticolesterolemiantes/administração & dosagem , Anticolesterolemiantes/síntese química , Colesterol/sangue , Humanos , Ligantes , Espectroscopia de Ressonância Magnética , Proteínas de Membrana Transportadoras/metabolismo , Simulação de Acoplamento Molecular , Piridinas/química , Estereoisomerismo
14.
Int J Mol Sci ; 22(11)2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34072169

RESUMO

Highly functional macromolecules with a well-defined architecture are the key to designing efficient and smart materials, and these polymeric systems can be tailored for specific applications in a diverse range of fields. Herein, the formation of a new liquid crystalline polymeric network based on the crosslinking of dendrimeric entities by the CuI-catalyzed variant of the Huisgen 1,3-dipolar cycloaddition of azides and alkynes to afford 1,2,3-triazoles is reported. The polymeric material obtained in this way is easy to process and exhibits a variety of properties, which include mesomorphism, viscoelastic behavior, and thermal contraction. The porous microstructure of the polymer network determines its capability to absorb solvent molecules and to encapsulate small molecules, like organic dyes, which can be released easily afterwards. Moreover, all these properties may be easily tuned by modifying the chemical structure of the constituent dendrimers, which makes this system a very interesting one for a number of applications.


Assuntos
Dendrímeros/química , Cristais Líquidos/química , Polímeros/química , Algoritmos , Fenômenos Químicos , Técnicas de Química Sintética , Cristais Líquidos/ultraestrutura , Fenômenos Mecânicos , Modelos Teóricos , Estrutura Molecular , Difração de Raios X
15.
Int J Mol Sci ; 22(11)2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34071854

RESUMO

Metastatic castration-resistant prostate cancer (mCRPC) is a progressive and incurable disease with poor prognosis for patients. Despite introduction of novel therapies, the mortality rate remains high. An attractive alternative for extension of the life of mCRPC patients is PSMA-based targeted radioimmunotherapy. In this paper, we extended our in vitro study of 223Ra-labeled and PSMA-targeted NaA nanozeolites [223RaA-silane-PEG-D2B] by undertaking comprehensive preclinical in vitro and in vivo research. The toxicity of the new compound was evaluated in LNCaP C4-2, DU-145, RWPE-1 and HPrEC prostate cells and in BALB/c mice. The tissue distribution of 133Ba- and 223Ra-labeled conjugates was studied at different time points after injection in BALB/c and LNCaP C4-2 tumor-bearing BALB/c Nude mice. No obvious symptoms of antibody-free and antibody-functionalized nanocarriers cytotoxicity and immunotoxicity was found, while exposure to 223Ra-labeled conjugates resulted in bone marrow fibrosis, decreased the number of WBC and platelets and elevated serum concentrations of ALT and AST enzymes. Biodistribution studies revealed high accumulation of 223Ra-labeled conjugates in the liver, lungs, spleen and bone tissue. Nontargeted and PSMA-targeted radioconjugates exhibited a similar, marginal uptake in tumour lesions. In conclusion, despite the fact that NaA nanozeolites are safe carriers, the intravenous administration of NaA nanozeolite-based radioconjugates is dubious due to its high accumulation in the lungs, liver, spleen and bones.


Assuntos
Imunoconjugados/farmacocinética , Nanopartículas , Neoplasias da Próstata/terapia , Compostos Radiofarmacêuticos/farmacocinética , Rádio (Elemento) , Nanomedicina Teranóstica , Zeolitas , Animais , Anticorpos Monoclonais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 7/metabolismo , Linhagem Celular Tumoral , Fenômenos Químicos , Técnicas de Química Sintética , Modelos Animais de Doenças , Desenho de Fármacos , Perfilação da Expressão Gênica , Humanos , Imunoconjugados/administração & dosagem , Imunoconjugados/efeitos adversos , Marcação por Isótopo , Masculino , Camundongos , Camundongos Nus , Estrutura Molecular , Nanopartículas/química , Neoplasias da Próstata/diagnóstico , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/efeitos adversos , Compostos Radiofarmacêuticos/química , Rádio (Elemento)/química , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto , Zeolitas/química
16.
Int J Mol Sci ; 22(11)2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34072234

RESUMO

A silica-bound C-butylpyrogallol[4]arene chromatographic stationary phase was prepared and characterised by thermogravimetric analysis, scanning electron microscopy, NMR and mass spectrometry. The chromatographic performance was investigated by using C60 and C70 fullerenes in reverse phase mode via flash column and high-pressure liquid chromatography (HPLC). The resulting new stationary phase was observed to demonstrate size-selective molecular recognition as postulated from our in-silico studies. The silica-bound C-butylpyrogallol[4]arene flash and HPLC stationary phases were able to separate a C60- and C70-fullerene mixture more effectively than an RP-C18 stationary phase. The presence of toluene in the mobile phase plays a significant role in achieving symmetrical peaks in flash column chromatography.


Assuntos
Cromatografia em Gel/métodos , Cromatografia Líquida de Alta Pressão/métodos , Fulerenos/química , Fulerenos/isolamento & purificação , Técnicas de Química Sintética , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Teoria Quântica , Dióxido de Silício/química , Termogravimetria
17.
Int J Nanomedicine ; 16: 3599-3612, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34079252

RESUMO

Purpose: Vernonia amygdalina (VA) is a traditional African herbal medicine that has been reported to possess anticancer properties. However, the anticancer properties of VA silver nanoparticles have not been studied. The aim of the study was to examine and evaluate the anticancer activities of VA leaf extracts and VA silver nanoparticles on the human breast cancer cell line, MCF-7. Methods: VA leaves were extracted using sequential extraction assisted with ultrasound using three different solvents: ethanol, 50% ethanol, and deionized water. The silver nanoparticles were synthesised with VA aqueous extract. Results: The ethanol extract and VA silver nanoparticles inhibit MCF-7 cell proliferation with an average half-maximal inhibitory concentration (IC50) value of 67µg/mL and 6.11µg/mL, respectively, after 72 hours of treatment. The ethanol extract and VA silver nanoparticles also caused G1 phase cell cycle arrest, induced apoptosis and nuclear fragmentation in MCF-7 cells. Conclusion: VA ethanol extracts and VA silver nanoparticles decreased the cell viability in MCF-7 cells in a time and dose-dependent manner by inducing apoptosis and causing DNA damage. Further research is needed to elucidate the mechanism of action of VA leaf extracts and VA silver nanoparticles. This study is the first to report on the anticancer activity of VA silver nanoparticles in MCF-7 cells.


Assuntos
Nanopartículas Metálicas , Extratos Vegetais/química , Folhas de Planta/química , Prata/química , Prata/farmacologia , Vernonia/química , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Química Sintética , Dano ao DNA , Química Verde , Humanos , Células MCF-7 , Solventes/química
18.
Life Sci ; 278: 119647, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34043990

RESUMO

Recently, the dramatic emergence of antimicrobial resistance has received attention from World Health Organization. Synthetic antimicrobial peptides (SAMPs) are considered new weapons to fight against infections caused by multi-drug resistant pathogens. Here, the authors provide an overview of the current research on SAMPs. The focus is SAMPs, how to design them, which features must be considered during design, and comparison with natural peptides. This review also includes a discussion about the natural AMPs, mechanisms of action and applications as new drugs or even as adjuvants molecules to enhance commercial drugs activity. The advances in chemical synthesis have reduced the cost to produce synthetic peptides open ways to achieve new antimicrobial agents. Therefore, synthetic peptides are new promising molecules to safeguard human and animal health.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Desenho de Fármacos , Resistência Microbiana a Medicamentos , Proteínas Citotóxicas Formadoras de Poros/química , Proteínas Citotóxicas Formadoras de Poros/farmacologia , Animais , Anti-Infecciosos/síntese química , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Técnicas de Química Sintética , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Fungos/efeitos dos fármacos , Humanos , Micoses/tratamento farmacológico , Proteínas Citotóxicas Formadoras de Poros/síntese química
19.
Molecules ; 26(9)2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: covidwho-1217103

RESUMO

The outbreak of SARS-CoV-2 has drastically changed our everyday life and the life of scientists from all over the world. In the last year, the scientific community has faced this worldwide threat using any tool available in order to find an effective response. The recent formulation, production, and ongoing administration of vaccines represent a starting point in the battle against SARS-CoV-2, but they cannot be the only aid available. In this regard, the use of drugs capable to mitigate and fight the virus is a crucial aspect of the pharmacological strategy. Among the plethora of approved drugs, a consistent element is a heterocyclic framework inside its skeleton. Heterocycles have played a pivotal role for decades in the pharmaceutical industry due to their high bioactivity derived from anticancer, antiviral, and anti-inflammatory capabilities. In this context, the development of new performing and sustainable synthetic strategies to obtain heterocyclic molecules has become a key focus of scientists. In this review, we present the recent trends in metal-promoted heterocyclization, and we focus our attention on the construction of heterocycles associated with the skeleton of drugs targeting SARS-CoV-2 coronavirus.


Assuntos
Antivirais/farmacologia , COVID-19/tratamento farmacológico , Técnicas de Química Sintética/métodos , Compostos Heterocíclicos/farmacologia , SARS-CoV-2/efeitos dos fármacos , Antivirais/síntese química , Antivirais/química , COVID-19/virologia , Catálise , Proteases 3C de Coronavírus/antagonistas & inibidores , Proteases 3C de Coronavírus/metabolismo , Compostos Heterocíclicos/síntese química , Compostos Heterocíclicos/química , Humanos , Metais/química , Inibidores de Proteases/síntese química , Inibidores de Proteases/química , Inibidores de Proteases/farmacologia , SARS-CoV-2/metabolismo
20.
Int J Nanomedicine ; 16: 3091-3103, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33953557

RESUMO

Objective: To synthesize and determine the antifungal activity of AgBr-nanoparticles (NP) @CTMAB (cetyltrimethyl-ammonium bromide) against Candida albicans (C. albicans) for use in the field of denture cleaning. Methods: The morphology and structure of AgBr-NP@CTMAB were characterized by IR, UV-Vis, XRD and SEM. The antifungal potential of AgBr-NP@CTMAB against C. albicans was determined by colony formation assay and growth curve analysis. PMMA containing AgBr-NP@CTMAB was prepared, and the long-term antifungal efficacy was analyzed. The effect against C. albicans biofilm was analyzed by SEM and OD600 , and the color changes of the specimens were observed by stereomicroscopy after 1 week of incubation. Cytotoxicity to human oral gingival fibroblasts and oral mucosal epithelial cells was detected by Cell Counting Kit-8 (CCK-8) in vitro. Results: The compound showed a good crystalline phase, the presence of AgBr nanoparticles and the hybridization of CTMAB+ with AgBr-NPs. AgBr-NP@CTMAB showed significant antifungal activity against C. albicans at concentrations of 10 µg/mL and 20 µg/mL. PMMA specimens containing AgBr-NP@CTMAB showed no long-term antifungal effect against C. albicans biofilm. The clearance rate of C. albicans attached to PMMA was 44.73% after soaking in 10 µg/mL AgBr-NP@CTMAB solution for 30 min and 91.35% for 8 h. There was no significant residual cytotoxicity or visual color change after soaking. Significance: AgBr-NP@CTMAB showed promising potential treatment for denture cleaners.


Assuntos
Antifúngicos/síntese química , Antifúngicos/farmacologia , Cetrimônio/química , Nanopartículas/química , Polimetil Metacrilato/química , Antifúngicos/química , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Candida albicans/fisiologia , Técnicas de Química Sintética , Humanos , Nanotecnologia
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