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1.
Molecules ; 26(11)2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34199336

RESUMO

The natural compound ravenelin was isolated from the biomass extracts of Exserohilum rostratum fungus, and its antimicrobial, antiplasmodial, and trypanocidal activities were evaluated. Ravenelin was isolated by column chromatography and HPLC and identified by NMR and MS. The susceptibility of Gram-positive and Gram-negative bacteria strains to ravenelin was determined by microbroth dilution assay. Cytotoxicity was evaluated in hepatocarcinoma cells (HepG2) and BALB/c peritoneal macrophages by using MTT. SYBR Green I-based assay was used in the asexual stages of Plasmodium falciparum. Trypanocidal activity was tested against the epimastigote and intracellular amastigote forms of Trypanosoma cruzi. Ravenelin was active against Gram-positive bacteria strains, with emphasis on Bacillus subtilis (MIC value of 7.5 µM). Ravenelin's antiparasitic activities were assessed against both the epimastigote (IC50 value of 5 ± 1 µM) and the intracellular amastigote forms of T. cruzi (IC50 value of 9 ± 2 µM), as well as against P. falciparum (IC50 value of 3.4 ± 0.4 µM). Ravenelin showed low cytotoxic effects on both HepG2 (CC50 > 50 µM) and peritoneal macrophage (CC50 = 185 ± 1 µM) cells with attractive selectivity for the parasites (SI values > 15). These findings indicate that ravenelin is a natural compound with both antibacterial and antiparasitic activities, and considerable selectivity indexes. Therefore, ravenelin is an attractive candidate for hit-to-lead development.


Assuntos
Antibacterianos/farmacologia , Antiprotozoários/farmacologia , Ascomicetos/química , Macrófagos Peritoneais/citologia , Xantonas/farmacologia , Animais , Antibacterianos/química , Antiprotozoários/química , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Biomassa , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cromatografia Líquida de Alta Pressão , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Células Hep G2 , Humanos , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/parasitologia , Espectroscopia de Ressonância Magnética , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Estrutura Molecular , Plasmodium falciparum/efeitos dos fármacos , Trypanosoma cruzi/efeitos dos fármacos , Xantonas/química
2.
Molecules ; 26(12)2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34205312

RESUMO

In the current study, in vitro antimicrobial and antioxidant activities and in vivo anti-inflammatory and analgesic activities of Scutellaria edelbergii Rech. f. (crude extract and subfractions, i.e., n-hexane, ethyl acetate (EtOAc), chloroform, n-butanol (n-BuOH) and aqueous) were explored. Initially, extraction and fractionation of the selected medicinal plant were carried out, followed by phytochemical qualitative tests, which were mostly positive for all the extracts. EtOAc fraction possessed a significant amount of phenolic (79.2 ± 0.30 mg GAE/g) and flavonoid (84.0 ± 0.39 mg QE/g) content. The EtOAc fraction of S. edelbergii exhibited appreciable antibacterial activity against Gram-negative (Escherichia coli and Klebsiella pneumoniae) strains and significant zones of inhibition were observed against Gram-positive bacterial strains (Bacillus subtilis and Staphylococcus aureus). However, it was found inactive against Candida Albicans and Fusarium oxysporum fungal strains. The chloroform fraction was the most effective with an IC50 value of 172 and 74 µg/mL against DPPH (1,1-Diphenyl-2-picryl-hydrazyl) and ABTS assays, in comparison with standard ascorbic acid 59 and 63 µg/mL, respectively. Moreover, the EtOAc fraction displayed significant in vivo anti-inflammatory activity (54%) using carrageenan-induced assay and significant (55%) in vivo analgesic activity using acetic acid-induced writing assay. In addition, nine known compounds, ursolic acid (UA), ovaul (OV), oleanolic acid (OA), ß-sitosterol (BS), micromeric acid (MA), taraxasterol acetate (TA), 5,3',4'-trihydroxy-7-methoxy flavone (FL-1), 5,7,4'-trihydroxy-6,3'-dimiethoxyflavone (FL-2) and 7-methoxy catechin (FL-3), were isolated from methanolic extract of S. edelbergii. These constituents have never been obtained from this source. The structures of all the isolated constituents were elucidated by spectroscopic means. In conclusion, the EtOAc fraction and all other fractions of S. edelbergii, in general, displayed a significant role as antibacterial, free radical scavenger, anti-inflammatory and analgesic agents which may be due to the presence of these constituents and other flavonoids.


Assuntos
Extratos Vegetais/farmacologia , Scutellaria/química , Antibacterianos/química , Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Antifúngicos/farmacologia , Antioxidantes/farmacologia , Pesquisa Biomédica/métodos , Flavonoides/farmacologia , Fungos/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Fenóis/farmacologia , Compostos Fitoquímicos/farmacologia , Plantas Medicinais/química
3.
Int J Mol Sci ; 22(9)2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-34063691

RESUMO

The constantly growing resistance of bacteria to antibiotics and other antibacterial substances has led us to an era in which alternative antimicrobial therapies are urgently required. One promising approach is to target bacterial pathogens using metal complexes. Therefore, we investigated the possibility of utilizing series of manganese(II) complexes with heteroaromatic ligands: Alcohol, aldehyde, ketone, and carboxylic acid as inhibitors for biofilm formation of Pseudomonas aeruginosa. To complete the series mentioned above, Mn-dipyCO-NO3 with dipyridin-2-ylmethanone (dipyCO) was isolated, and then structurally (single-crystal X-ray analysis) and physicochemically characterized (FT-IR, TG, CV, magnetic susceptibility). The antibacterial activity of the compounds against representative Gram-negative and Gram-positive bacteria was also evaluated. It is worth highlighting that the results of the cytotoxicity assays performed (MTT, DHI HoloMonitorM4) indicate high cell viability of the human fibroblast (VH10) in the presence of the Mn(II) complexes. Additionally, the inhibition effect of catalase activity by the complexes was studied. This paper focused on such aspects as studying different types of intermolecular interactions in the crystals of the Mn(II) complexes as well as their possible effect on anti-biofilm activity, the structure-activity relationship of the Mn(II) complexes, and regularity between the electrochemical properties of the Mn(II) complexes and anti-biofilm activity.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Complexos de Coordenação/química , Manganês/química , Álcoois/química , Aldeídos/química , Antibacterianos/química , Ácidos Carboxílicos/química , Complexos de Coordenação/farmacologia , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Cetonas/química , Testes de Sensibilidade Microbiana , Oxirredução/efeitos dos fármacos , Pseudomonas aeruginosa , Espectroscopia de Infravermelho com Transformada de Fourier
4.
Molecules ; 26(10)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065282

RESUMO

The incidence of antibiotic resistance in pathogenic bacteria has become an alarming clinical and social problem. Therefore, the demand for alternative antimicrobial compounds has increased. In this study, a chemical profile of honey bee (Apis mellifera L.) venom (HBV) has been determined by HPLC and FTIR-ATR spectroscopy, and tested for antibacterial activity, as well as efficiency with regard to conventional antibiotics. The investigated HBV was of high quality with melittin and total protein contents of 70.10 ± 7.01%, and 84.44 ± 3.12 g/100 g, respectively. The purity of HBV was confirmed by FTIR-ATR spectral profiling, which revealed a unique pattern of absorption bands that are characteristic of its major fractions. In addition, HBV showed a broad spectrum of activity against all three tested biomasses of potentially pathogenic Gram-positive and Gram-negative bacteria with MIC values ranging between 12.5 and 200 µg/mL, and MBC between 12.5 and 400 µg/mL. When compared to conventional antibiotics, HBV (400 µg) showed up to 27.8% efficiency of tetracycline (30 µg), 52.2% erythromycin (15 µg), 21.2% ciprofloxacin (5 µg), and 34.6% of ampicillin-sulbactam (20 µg). The overall results demonstrate the therapeutic potential of the analyzed HBV.


Assuntos
Anti-Infecciosos/farmacologia , Venenos de Abelha/química , Venenos de Abelha/farmacologia , Animais , Abelhas , Cromatografia Líquida de Alta Pressão/métodos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Espectroscopia de Infravermelho com Transformada de Fourier/métodos
5.
Toxins (Basel) ; 13(5)2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-34064808

RESUMO

Scorpion venoms are rich resources of antimicrobial peptides (AMPs). While the short-chain noncysteine-containing AMPs have attracted much attention as templates for drug development, the antimicrobial potential of long-chain noncysteine-containing AMPs has been largely overlooked. Here, by using the online HeliQuest server, we designed and analyzed a series of 14-residue fragments of Smp43, a 43-residue long-chain noncysteine-containing AMP identified from the venom of Scorpio maurus palmatus. We found that Smp43(1-14) shows high antimicrobial activity against both Gram-positive and Gram-negative bacteria and is nontoxic to mammalian cells at the antimicrobial dosage. Sequence alignments showed that the designed Smp43(1-14) displays a unique primary structure that is different from other natural short-chain noncysteine-containing AMPs from scorpions, such as Uy17, Uy192 and IsCT. Moreover, the peptide Smp43(1-14) caused concentration-dependent fluorescence increases in the bacteria for all of the tested dyes, propidium iodide, SYTOXTM Green and DiSC3-5, suggesting that the peptide may kill the bacteria through the formation of pore structures in the plasma membrane. Taken together, our work sheds light on a new avenue for the design of novel short-chain noncysteine-containing AMPs and provides a good peptide template with a unique sequence for the development of novel drugs for use against bacterial infectious diseases.


Assuntos
Antibacterianos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Proteínas Citotóxicas Formadoras de Poros/farmacologia , Venenos de Escorpião/química , Animais , Antibacterianos/isolamento & purificação , Membrana Celular/metabolismo , Proteínas Citotóxicas Formadoras de Poros/isolamento & purificação , Conformação Proteica em alfa-Hélice , Escorpiões
6.
Nat Commun ; 12(1): 3577, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-34117249

RESUMO

Target protection proteins confer resistance to the host organism by directly binding to the antibiotic target. One class of such proteins are the antibiotic resistance (ARE) ATP-binding cassette (ABC) proteins of the F-subtype (ARE-ABCFs), which are widely distributed throughout Gram-positive bacteria and bind the ribosome to alleviate translational inhibition from antibiotics that target the large ribosomal subunit. Here, we present single-particle cryo-EM structures of ARE-ABCF-ribosome complexes from three Gram-positive pathogens: Enterococcus faecalis LsaA, Staphylococcus haemolyticus VgaALC and Listeria monocytogenes VgaL. Supported by extensive mutagenesis analysis, these structures enable a general model for antibiotic resistance mediated by these ARE-ABCFs to be proposed. In this model, ABCF binding to the antibiotic-stalled ribosome mediates antibiotic release via mechanistically diverse long-range conformational relays that converge on a few conserved ribosomal RNA nucleotides located at the peptidyltransferase center. These insights are important for the future development of antibiotics that overcome such target protection resistance mechanisms.


Assuntos
Antibacterianos/farmacologia , Diterpenos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Lincosamidas/farmacologia , Compostos Policíclicos/farmacologia , Estreptograminas/farmacologia , Transportadores de Cassetes de Ligação de ATP/química , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Adesinas Bacterianas/química , Adesinas Bacterianas/genética , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Sítios de Ligação , Microscopia Crioeletrônica , Farmacorresistência Bacteriana/genética , Bactérias Gram-Positivas/genética , Modelos Moleculares , Peptidil Transferases/metabolismo , Conformação Proteica , RNA Mensageiro , Ribossomos/metabolismo
7.
Biomolecules ; 11(5)2021 05 17.
Artigo em Inglês | MEDLINE | ID: covidwho-1234665

RESUMO

Cm-p5 is a snail-derived antimicrobial peptide, which demonstrated antifungal activity against the pathogenic strains of Candida albicans. Previously we synthetized a cyclic monomer as well as a parallel and an antiparallel dimer of Cm-p5 with improved antifungal activity. Considering the alarming increase of microbial resistance to conventional antibiotics, here we evaluated the antimicrobial activity of these derivatives against multiresistant and problematic bacteria and against important viral agents. The three peptides showed a moderate activity against Pseudomonas aeruginosa, Klebsiella pneumoniae Extended Spectrum ß-Lactamase (ESBL), and Streptococcus agalactiae, with MIC values > 100 µg/mL. They exerted a considerable activity with MIC values between 25-50 µg/mL against Acinetobacter baumanii and Enterococcus faecium. In addition, the two dimers showed a moderate activity against Pseudomonas aeruginosa PA14. The three Cm-p5 derivatives inhibited a virulent extracellular strain of Mycobacterium tuberculosis, in a dose-dependent manner. Moreover, they inhibited Herpes Simplex Virus 2 (HSV-2) infection in a concentration-dependent manner, but had no effect on infection by the Zika Virus (ZIKV) or pseudoparticles of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2). At concentrations of >100 µg/mL, the three new Cm-p5 derivatives showed toxicity on different eukaryotic cells tested. Considering a certain cell toxicity but a potential interesting activity against the multiresistant strains of bacteria and HSV-2, our compounds require future structural optimization.


Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Antivirais/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Herpesvirus Humano 2/efeitos dos fármacos , Sequência de Aminoácidos , Animais , Antibacterianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Antivirais/química , Candida albicans/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dimerização , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , SARS-CoV-2/efeitos dos fármacos
8.
Sci Rep ; 11(1): 12410, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: covidwho-1268005

RESUMO

In situ generation of antibacterial and antiviral agents by harnessing the catalytic activity of enzymes on surfaces provides an effective eco-friendly approach for disinfection. The perhydrolase (AcT) from Mycobacterium smegmatis catalyzes the perhydrolysis of acetate esters to generate the potent disinfectant, peracetic acid (PAA). In the presence of AcT and its two substrates, propylene glycol diacetate and H2O2, sufficient and continuous PAA is generated over an extended time to kill a wide range of bacteria with the enzyme dissolved in aqueous buffer. For extended self-disinfection, however, active and stable AcT bound onto or incorporated into a surface coating is necessary. In the current study, an active, stable and reusable AcT-based coating was developed by incorporating AcT into a polydopamine (PDA) matrix in a single step, thereby forming a biocatalytic composite onto a variety of surfaces. The resulting AcT-PDA composite coatings on glass, metal and epoxy surfaces yielded up to 7-log reduction of Gram-positive and Gram-negative bacteria when in contact with the biocatalytic coating. This composite coating also possessed potent antiviral activity, and dramatically reduced the infectivity of a SARS-CoV-2 pseudovirus within minutes. The single-step approach enables rapid and facile fabrication of enzyme-based disinfectant composite coatings with high activity and stability, which enables reuse following surface washing. As a result, this enzyme-polymer composite technique may serve as a general strategy for preparing antibacterial and antiviral surfaces for applications in health care and common infrastructure safety, such as in schools, the workplace, transportation, etc.


Assuntos
Antibacterianos/química , Antivirais/química , Proteínas de Bactérias/química , Hidrolases/química , Indóis/química , Polímeros/química , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Antivirais/metabolismo , Antivirais/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , COVID-19/patologia , COVID-19/virologia , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/metabolismo , Materiais Revestidos Biocompatíveis/farmacologia , Estabilidade de Medicamentos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Hidrolases/genética , Hidrolases/metabolismo , Cinética , Mycobacterium smegmatis/enzimologia , Ácido Peracético/metabolismo , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , SARS-CoV-2/efeitos dos fármacos
9.
Biomolecules ; 11(5)2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-34067685

RESUMO

Cm-p5 is a snail-derived antimicrobial peptide, which demonstrated antifungal activity against the pathogenic strains of Candida albicans. Previously we synthetized a cyclic monomer as well as a parallel and an antiparallel dimer of Cm-p5 with improved antifungal activity. Considering the alarming increase of microbial resistance to conventional antibiotics, here we evaluated the antimicrobial activity of these derivatives against multiresistant and problematic bacteria and against important viral agents. The three peptides showed a moderate activity against Pseudomonas aeruginosa, Klebsiella pneumoniae Extended Spectrum ß-Lactamase (ESBL), and Streptococcus agalactiae, with MIC values > 100 µg/mL. They exerted a considerable activity with MIC values between 25-50 µg/mL against Acinetobacter baumanii and Enterococcus faecium. In addition, the two dimers showed a moderate activity against Pseudomonas aeruginosa PA14. The three Cm-p5 derivatives inhibited a virulent extracellular strain of Mycobacterium tuberculosis, in a dose-dependent manner. Moreover, they inhibited Herpes Simplex Virus 2 (HSV-2) infection in a concentration-dependent manner, but had no effect on infection by the Zika Virus (ZIKV) or pseudoparticles of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2). At concentrations of >100 µg/mL, the three new Cm-p5 derivatives showed toxicity on different eukaryotic cells tested. Considering a certain cell toxicity but a potential interesting activity against the multiresistant strains of bacteria and HSV-2, our compounds require future structural optimization.


Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Antivirais/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Herpesvirus Humano 2/efeitos dos fármacos , Sequência de Aminoácidos , Animais , Antibacterianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Antivirais/química , Candida albicans/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dimerização , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , SARS-CoV-2/efeitos dos fármacos
10.
Int J Mol Sci ; 22(11)2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34073939

RESUMO

An amphipathic α-helical peptide, Hp1404, was isolated from the venomous gland of the scorpion Heterometrus petersii. Hp1404 exhibits antimicrobial activity against methicillin-resistant Staphylococcus aureus but is cytotoxic. In this study, we designed antimicrobial peptides by substituting amino acids at the 14 C-terminal residues of Hp1404 to reduce toxicity and improve antibacterial activity. The analog peptides, which had an amphipathic α-helical structure, were active against gram-positive and gram-negative bacteria, particularly multidrug-resistant Acinetobacter baumannii, and showed lower cytotoxicity than Hp1404. N-phenyl-1-naphthylamine uptake and DisC3-5 assays demonstrated that the peptides kill bacteria by effectively permeating the outer and cytoplasmic membranes. Additionally, the analog peptides inhibited biofilm formation largely than Hp1404 at low concentrations. These results suggest that the analog peptides of Hp1404 can be used as therapeutic agents against A. baumannii infection.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Escorpiões/química , 1-Naftilamina/análogos & derivados , 1-Naftilamina/metabolismo , Animais , Peptídeos Catiônicos Antimicrobianos/efeitos adversos , Peptídeos Catiônicos Antimicrobianos/química , Benzotiazóis/metabolismo , Biofilmes/efeitos dos fármacos , Carbocianinas/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Dicroísmo Circular , Escherichia coli/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Listeria monocytogenes/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Conformação Proteica em alfa-Hélice , Pseudomonas aeruginosa/efeitos dos fármacos , Salmonella/efeitos dos fármacos
11.
Molecules ; 26(10)2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34067859

RESUMO

A chalcone series (3a-f) with electron push-pull effect was synthesized via a one-pot Claisen-Schmidt reaction with a simple purification step. The compounds exhibited strong emission, peaking around 512-567 nm with mega-stokes shift (∆λ = 93-139 nm) in polar solvents (DMSO, MeOH, and PBS) and showed good photo-stability. Therefore, 3a-f were applied in cellular imaging. After 3 h of incubation, green fluorescence was clearly brighter in cancer cells (HepG2) compared to normal cells (HEK-293), suggesting preferential accumulation in cancer cells. Moreover, all compounds exhibited higher cytotoxicity within 24 h toward cancer cells (IC50 values ranging from 45 to 100 µM) than normal cells (IC50 value >100 µM). Furthermore, the antimicrobial properties of chalcones 3a-f were investigated. Interestingly, 3a-f exhibited antibacterial activities against Escherichia coli and Staphylococcus aureus, with minimum bactericidal concentrations (MBC) of 0.10-0.60 mg/mL (375-1000 µM), suggesting their potential antibacterial activity against both Gram-negative and Gram-positive bacteria. Thus, this series of chalcone-derived fluorescent dyes with facile synthesis shows great potential for the development of antibiotics and cancer cell staining agents.


Assuntos
Chalcona/química , Chalcona/síntese química , Corantes Fluorescentes/síntese química , Antibacterianos/farmacologia , Chalcona/isolamento & purificação , Chalconas/química , Chalconas/isolamento & purificação , Chalconas/farmacologia , Escherichia coli/efeitos dos fármacos , Fluorescência , Corantes Fluorescentes/química , Corantes Fluorescentes/uso terapêutico , Bactérias Gram-Positivas/efeitos dos fármacos , Células HEK293 , Células Hep G2 , Humanos , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-Atividade
12.
Sci Rep ; 11(1): 12410, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-34127732

RESUMO

In situ generation of antibacterial and antiviral agents by harnessing the catalytic activity of enzymes on surfaces provides an effective eco-friendly approach for disinfection. The perhydrolase (AcT) from Mycobacterium smegmatis catalyzes the perhydrolysis of acetate esters to generate the potent disinfectant, peracetic acid (PAA). In the presence of AcT and its two substrates, propylene glycol diacetate and H2O2, sufficient and continuous PAA is generated over an extended time to kill a wide range of bacteria with the enzyme dissolved in aqueous buffer. For extended self-disinfection, however, active and stable AcT bound onto or incorporated into a surface coating is necessary. In the current study, an active, stable and reusable AcT-based coating was developed by incorporating AcT into a polydopamine (PDA) matrix in a single step, thereby forming a biocatalytic composite onto a variety of surfaces. The resulting AcT-PDA composite coatings on glass, metal and epoxy surfaces yielded up to 7-log reduction of Gram-positive and Gram-negative bacteria when in contact with the biocatalytic coating. This composite coating also possessed potent antiviral activity, and dramatically reduced the infectivity of a SARS-CoV-2 pseudovirus within minutes. The single-step approach enables rapid and facile fabrication of enzyme-based disinfectant composite coatings with high activity and stability, which enables reuse following surface washing. As a result, this enzyme-polymer composite technique may serve as a general strategy for preparing antibacterial and antiviral surfaces for applications in health care and common infrastructure safety, such as in schools, the workplace, transportation, etc.


Assuntos
Antibacterianos/química , Antivirais/química , Proteínas de Bactérias/química , Hidrolases/química , Indóis/química , Polímeros/química , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Antivirais/metabolismo , Antivirais/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , COVID-19/patologia , COVID-19/virologia , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/metabolismo , Materiais Revestidos Biocompatíveis/farmacologia , Estabilidade de Medicamentos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Hidrolases/genética , Hidrolases/metabolismo , Cinética , Mycobacterium smegmatis/enzimologia , Ácido Peracético/metabolismo , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , SARS-CoV-2/efeitos dos fármacos
13.
Food Chem ; 360: 130036, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34004594

RESUMO

This study aimed to investigate the antibacterial efficiency and synergistic mechanisms of novel formulated eugenol-casein-lysozyme nanoparticles (ECL-NPs) against gram-positive bacteria. We obtained optimized ECL-NPs 151.9 nm in size and with an entrapment efficiency of 92.2%. ECL-NPs exhibited a satisfactory slow-release pattern, excellent storage stability (for 180 days at 4 °C), and freeze-drying stability. The synergy of low-dose lysozyme significantly enhanced the inhibitory efficiency of eugenol-casein nanoparticles against Staphylococcus aureus and Bacillus sp. by 5.83-fold and 5.53-fold, respectively; this resulted in a much lower minimum inhibitory concentration (3.75-fold and 4.16-fold) and minimum bacterial concentration (2.92-fold and 1.70-fold) values. Scanning electron microscopy clearly demonstrated that the entire cell morphological structure was broken into pieces after exposure to ECL-NPs. Furthermore, 100% microbial inhibition was observed in fresh fruits treated with ECL-NPs for 15 days. These findings suggest that ECL-NPs have an excellent potential for use in food industry against gram-positive bacteria.


Assuntos
Antibacterianos/farmacologia , Caseínas/química , Eugenol/química , Bactérias Gram-Positivas/efeitos dos fármacos , Muramidase/química , Anti-Infecciosos , Bacillus/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Nanopartículas/química , Staphylococcus aureus/efeitos dos fármacos
14.
Bioorg Chem ; 112: 104925, 2021 07.
Artigo em Inglês | MEDLINE | ID: covidwho-1198631

RESUMO

Antibiotic resistance and emerging viral pandemics have posed an urgent need for new anti-infective drugs. By screening our microbial extract library against the main protease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the notorious ESKAPE pathogens, an active fraction was identified and purified, leading to an initial isolation of adipostatins A (1) and B (2). In order to diversify the chemical structures of adipostatins toward enhanced biological activities, a type III polyketide synthase was identified from the native producer, Streptomyces davawensis DSM101723, and was subsequently expressed in an E. coli host, resulting in the isolation of nine additional adipostatins 3-11, including two new analogs (9 and 11). The structures of 1-11 were established by HRMS, NMR, and chemical derivatization, including using a microgram-scale meta-chloroperoxybenzoic acid epoxidation-MS/MS analysis to unambiguously determine the double bond position in the alkyl chain. The present study discovered SARS-CoV-2 main protease inhibitory activity for the class of adipostatins for the first time. Several of the adipostatins isolated also exhibited antimicrobial activity against selected ESKAPE pathogens.


Assuntos
Aciltransferases/metabolismo , Anti-Infecciosos/química , Proteínas de Bactérias/metabolismo , Resorcinóis/química , Aciltransferases/antagonistas & inibidores , Aciltransferases/classificação , Aciltransferases/genética , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/metabolismo , Anti-Infecciosos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/classificação , Proteínas de Bactérias/genética , COVID-19/patologia , COVID-19/virologia , Proteases 3C de Coronavírus/antagonistas & inibidores , Proteases 3C de Coronavírus/metabolismo , Avaliação Pré-Clínica de Medicamentos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Conformação Molecular , Filogenia , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Resorcinóis/isolamento & purificação , Resorcinóis/metabolismo , Resorcinóis/farmacologia , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/metabolismo , Streptomyces/enzimologia , Espectrometria de Massas em Tandem
15.
J Med Chem ; 64(11): 7630-7645, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-34009979

RESUMO

A class of quinazolone thiazoles was identified as new structural scaffolds for potential antibacterial conquerors to tackle dreadful resistance. Some prepared compounds exhibited favorable bacteriostatic efficiencies on tested bacteria, and the most representative 5j featuring the 4-trifluoromethylphenyl group possessed superior performances against Escherichia coli and Pseudomonas aeruginosa to norfloxacin. Further studies revealed that 5j with inappreciable hemolysis could hinder the formation of bacterial biofilms and trigger reactive oxygen species generation, which could take responsibility for emerging low resistance. Subsequent paralleled exploration discovered that 5j not only disintegrated outer and inner membranes to induce leakage of cytoplasmic contents but also broke the metabolism by suppressing dehydrogenase. Meanwhile, derivative 5j could intercalate into DNA to exert powerful antibacterial properties. Moreover, compound 5j gave synergistic effects against some Gram-negative bacteria in combination with norfloxacin. These findings indicated that this novel structural type of quinazolone thiazoles showed therapeutic foreground in struggling with Gram-negative bacterial infections.


Assuntos
Antibacterianos/farmacologia , Azóis/química , Bactérias Gram-Negativas/efeitos dos fármacos , Tiazóis/química , Antibacterianos/química , Antibacterianos/metabolismo , Membrana Externa Bacteriana/efeitos dos fármacos , Membrana Externa Bacteriana/metabolismo , Sítios de Ligação , Ligação Competitiva , Biofilmes/efeitos dos fármacos , Cristalografia por Raios X , Desenho de Fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Escherichia coli/fisiologia , Bactérias Gram-Positivas/efeitos dos fármacos , L-Lactato Desidrogenase/antagonistas & inibidores , L-Lactato Desidrogenase/metabolismo , Testes de Sensibilidade Microbiana , Conformação Molecular , Simulação de Acoplamento Molecular , Pseudomonas aeruginosa/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Tiazóis/metabolismo , Tiazóis/farmacologia
16.
Methods Mol Biol ; 2296: 59-75, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33977442

RESUMO

Extremophilic actinomycetes strains can survive extreme saline and alkaline environments and produce antimicrobial agents. In this chapter, we discuss laboratory methods that can be used to isolate and characterize actinomycetes strains capable of potentially producing novel antimicrobial agent(s) when cultured in conditions that mimic the environments from which they were isolated. Methods used to screen for antibacterial and antiviral activities from these producer strains, and microbiological and molecular approaches used to identify these strains are described. Here we describe three methods. Method 1 focuses on the strategy to select optimal conditions to synthesize and accumulate the antibiotics from the studied actinomycetes strains by preparing crude extracts. In Method 2, we describe the screening strategies used to test the actinomycetes strains against gram-negative and gram-positive bacteria, antifungal agents, multidrug-resistant pathogens (MDR), and viral pathogens. Thus, the specific techniques to test for MDR pathogens such as the disk diffusion assay and wells assay are outlined. We also describe the antiviral activity screening of the selected actinomycetes extracts in Method 2 of this chapter. Specifically, we concentrate on methods used to test for antiviral activities such as primary hemolytic, hemagglutination, neuraminidase, and specific virus-inhibitory activities. Finally, the Method 3 section reveals the microbiological techniques used to morphologically characterize the actinomycetes strains that depend on the culture medium utilized for growth. Additionally, the method used to perform a detailed characterization of the morphology that actinomycetes strains possess is specified by the protocol for sample preparation and visualization using the scanning electron microscopy (SEM). Finally, we summarize the molecular approaches used to characterize actinomycetes strains, focusing specifically on the PCR and sequencing techniques.


Assuntos
Actinobacteria/metabolismo , Anti-Infecciosos/metabolismo , Extremófilos/metabolismo , Anti-Infecciosos/farmacologia , Antivirais/metabolismo , Antivirais/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos
17.
Methods Mol Biol ; 2296: 143-149, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33977445

RESUMO

Screening extracts from the fermentation broth of a collection of actinomycetes can be performed conveniently on a microtiter plate format. Here we describe a method suited for the screening of antibacterial extracts or compounds against Gram-positive and Gram-negative aerobic, non-fastidious bacteria, Escherichia coli and Kocuria rhizophila. Both bacteria have been chosen to minimize the need for containment as they belong to risk group 1.


Assuntos
Actinobacteria/metabolismo , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Fermentação/fisiologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Testes de Sensibilidade Microbiana/métodos
18.
Bioorg Chem ; 112: 104925, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34022708

RESUMO

Antibiotic resistance and emerging viral pandemics have posed an urgent need for new anti-infective drugs. By screening our microbial extract library against the main protease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the notorious ESKAPE pathogens, an active fraction was identified and purified, leading to an initial isolation of adipostatins A (1) and B (2). In order to diversify the chemical structures of adipostatins toward enhanced biological activities, a type III polyketide synthase was identified from the native producer, Streptomyces davawensis DSM101723, and was subsequently expressed in an E. coli host, resulting in the isolation of nine additional adipostatins 3-11, including two new analogs (9 and 11). The structures of 1-11 were established by HRMS, NMR, and chemical derivatization, including using a microgram-scale meta-chloroperoxybenzoic acid epoxidation-MS/MS analysis to unambiguously determine the double bond position in the alkyl chain. The present study discovered SARS-CoV-2 main protease inhibitory activity for the class of adipostatins for the first time. Several of the adipostatins isolated also exhibited antimicrobial activity against selected ESKAPE pathogens.


Assuntos
Aciltransferases/metabolismo , Anti-Infecciosos/química , Proteínas de Bactérias/metabolismo , Resorcinóis/química , Aciltransferases/antagonistas & inibidores , Aciltransferases/classificação , Aciltransferases/genética , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/metabolismo , Anti-Infecciosos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/classificação , Proteínas de Bactérias/genética , COVID-19/patologia , COVID-19/virologia , Proteases 3C de Coronavírus/antagonistas & inibidores , Proteases 3C de Coronavírus/metabolismo , Avaliação Pré-Clínica de Medicamentos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Conformação Molecular , Filogenia , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Resorcinóis/isolamento & purificação , Resorcinóis/metabolismo , Resorcinóis/farmacologia , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/metabolismo , Streptomyces/enzimologia , Espectrometria de Massas em Tandem
19.
Molecules ; 26(7)2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33805524

RESUMO

The development of new materials is needed to address the environmental challenges of wastewater treatment. The phosphorylation of guar gum combined with its association to chitosan allows preparing an efficient sorbent for the removal of U(VI) from slightly acidic solutions. The incorporation of magnetite nanoparticles enhances solid/liquid. Functional groups are characterized by FTIR spectroscopy while textural properties are qualified by N2 adsorption. The optimum pH is close to 4 (deprotonation of amine and phosphonate groups). Uptake kinetics are fast (60 min of contact), fitted by a pseudo-first order rate equation. Maximum sorption capacities are close to 1.28 and 1.16 mmol U g-1 (non-magnetic and magnetic, respectively), while the sorption isotherms are fitted by Langmuir equation. Uranyl desorption (using 0.2 M HCl solutions) is achieved within 20-30 min; the sorbents can be recycled for at least five cycles (5-6% loss in sorption performance, complete desorption). In multi-component solutions, the sorbents show marked preference for U(VI) and Nd(III) over alkali-earth metals and Si(IV). The zone of exclusion method shows that magnetic sorbent has antibacterial effects against both Gram+ and Gram- bacteria, contrary to non-magnetic material (only Gram+ bacteria). The magnetic composite is highly promising as antimicrobial support and for recovery of valuable metals.


Assuntos
Quitosana/química , Galactanos/química , Nanopartículas de Magnetita/química , Mananas/química , Nanocompostos/química , Gomas Vegetais/química , Urânio/química , Purificação da Água/métodos , Adsorção , Antibacterianos/química , Antibacterianos/farmacologia , Bactérias Gram-Positivas/efeitos dos fármacos , Cinética , Fosforilação
20.
Int J Biol Macromol ; 181: 990-1002, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: covidwho-1188608

RESUMO

Coronaviruses (CoV) are a large family of viruses that cause illness ranging from the common cold to more severe diseases such as Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV). We succeeded in preparing disinfectant cellulose-based wipes treated with antimicrobial and antiviral silver nanoparticles to be used for prevention of contamination and transmission of several pathogenic viruses and microbes to human in critical areas such as hospitals and healthcare centers especially coronavirus. In this work, the antimicrobial and antiviral activities of silver nanoparticles (AgNPs) prepared with four different techniques were investigated for the utilization as a disinfectant for cellulose-based wipes. These four methods are namely; 1) trisodium citrate with cotton yarn as a reducing agent, 2) preparing AgNP's using aqueous solution of PVA in the presence of glucose, 3) trisodium citrate with cotton fabric as a reducing agent, and 4) photochemical reaction of polyacrylic acid and silver nitrate solution. Polyester/viscose blended spunlace nonwoven fabrics as cellulose based fabrics were treated with the prepared silver nanoparticles to be used as surfaces disinfection wipes. The properties of the nonwoven fabrics were examined including thickness, tensile strength in dry and wet conditions in both machine direction (MD) and cross-machine direction (CMD), bursting strength, air permeability, water permeability and surface wettability. Characterization of the AgNPs was carried out in terms of UV-VIS spectroscopy, TEM, SEM, and Zeta potential analysis. The assessment of AgNPs active solutions for antimicrobial and antiviral activities was evaluated. The results obtained from the analyses of the AgNPs samples prepared with different techniques showed good uniformity and stability of the particles, as well uniform coating of the AgNPs on the fibers. Additionally, there is a significant effect of the AgNPs preparation method on their disinfectant performance that proved its effectiveness against coronavirus (MERS-CoV), S. aureus and B. subtilis as Gram-positive bacteria, E. coli and P. mirabilis as Gram-negative bacteria, A. niger and C. albicans fungi.


Assuntos
COVID-19/prevenção & controle , Celulose/química , Coronavirus/efeitos dos fármacos , Desinfetantes/química , Nanopartículas Metálicas/química , SARS-CoV-2/efeitos dos fármacos , Prata/química , Resinas Acrílicas/química , Antibacterianos/química , Anti-Infecciosos/química , Antivirais/química , Citratos/química , Fibra de Algodão , Fungos/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Química Verde , Testes de Sensibilidade Microbiana , Nitrato de Prata/química
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