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1.
Nat Prod Res ; 37(12): 1947-1953, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35959682

RESUMO

Infectious diseases caused by viruses like HIV and SARS-COV-2 (COVID-19) pose serious public health threats. In search for new antiviral small molecules from chemically underexplored Hypericum species, a previously undescribed atropisomeric C8-C8' linked dimeric coumarin named bichromonol (1) was isolated from the stem bark of Hypericum roeperianum. The structure was elucidated by MS data and NMR spectroscopy. The absolute configuration at the biaryl axis was determined by comparing the experimental ECD spectrum with those calculated for the respective atropisomers. Bichromonol was tested in cell-based assays for cytotoxicity against MT-4 (CC50 = 54 µM) cells and anti-HIV activity in infected MT-4 cells. It exhibits significant activity at EC50 = 6.6-12.0 µM against HIV-1 wild type and its clinically relevant mutant strains. Especially, against the resistant variants A17 and EFVR, bichromonol is more effective than the commercial drug nevirapine and might thus have potential to serve as a new anti-HIV lead.


Assuntos
COVID-19 , Hypericum , Humanos , Hypericum/química , Casca de Planta , SARS-CoV-2 , Cumarínicos/química , Estrutura Molecular
2.
Pharmaceuticals (Basel) ; 15(2)2022 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-35215294

RESUMO

The Enterovirus genus includes many viruses that are pathogenic in humans, including Coxsackie viruses and rhinoviruses, as well as the emerging enteroviruses D68 and A71. Currently, effective antiviral agents are not available for the treatment or prevention of enterovirus infections, which remain an important threat to public health. We recently identified a series of quinoxaline derivatives that were provento be potent inhibitors of coxsackievirus B5, the most common and a very important human pathogen belonging to the enterovirus genus. We have shown how most active derivatives interfere with the earliest stages of viral replication, blocking infection. Considering the broad antiviral spectrum, a very attractive property for an antiviral drug, we aimed to investigate the antiviral activity of the most promising compounds against other Enterovirus species. Here, we investigated the susceptibility of a panel of representatives of Enterovirus genus (enterovirus A71, belonging to A species; coxsackieviruses B4 and B3;echovirus 9, belonging to B species; and enterovirus D68, belonging to D species) to quinoxaline inhibitors. We also tested cytotoxicity and selectivity indices of the selected compounds, as well as their effects on virus yield.We also investigated their potential mechanism of action by a time course assay. In addition, a bioinformatic analysis was carried out to discover potential new conserved motifs in CVB3 and CVB4 compared to the other enterovirus species that can be used as new targets.

3.
Pathogens ; 10(4)2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33805453

RESUMO

Plant products provide an alternative and successful source of lead compounds for the pharmaceutical industry. The present study was aimed to evaluate, in cell-based assays, the antiviral properties of essential oils obtained from plants that commonly grow in Sardinia, Italy, against a broad spectrum of RNA/DNA viruses. The essential oils of Helichrisumitalicum (Roth) G. Don ssp. microphyllum (Willd.) Nyman, Laurus nobilis L., Mirtuscommunis L., Pistacia lentiscus L., Salvia officinalis L., Saturejathymbra L., Lavandula angustifolia Mill., Foeniculum vulgare Mill., and Eucalyptus globulus Labill. were extracted by hydrodistillation and analyzed by gas chromatography mass spectrometry (GC-MS). Interestingly, the essential oil of Salvia officinalis showed moderate activity against bovine viral diarrhea virus (BVDV), an enveloped RNA virus belonging to the Flaviviridae family. BVDV is responsible for several clinical manifestations in bovines, including respiratory, gastroenteric, and reproductive diseases, with a significant economic impact. With the aim to individuate the constituent of the Salvia officinalis responsible for the biological activity, we tested the major components of the oil: camphene, ß-pinene, limonene, 1,8-cineole, cis-thujone, camphor, (E)-caryophyllene, and α-humulene. Here, we describe α-humulene as an active component that is non-cytotoxic and active against BVDV (EC50 = 36 µM). Its antiviral effects were evaluated using virucidal cytopathic effect inhibition and viral yield reduction assays. This is the first scientific report showing the anti BVDV effects of Salvia officinalis essential oil and α-humulene as the main active component.

4.
Microbiol Resour Announc ; 10(4)2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33509993

RESUMO

The genome sequences of 10 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains from Sliema, Malta, were obtained by Nanopore sequencing using the amplicon sequencing approach developed by the Artic Network. The assembled genomes were analyzed with Pangolin software and assigned to the B.1 lineage, which is widely circulating in Europe.

5.
Viruses ; 13(1)2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33406781

RESUMO

Enterovirus A71 (EV-A71) infection has emerged as a significant public health concern atthe global level. Epidemic events of EV-A71 have been reported worldwide, and this succession of outbreaks has heightened concern that EV-A71 may become a public health threat. In recent years, widespread A71 enterovirus also occurred in European countries. EV-A71 infection causes hand-foot-mouth disease (HFMD), herpangina, and fever. However, it can sometimes induce a variety of neurological complications, including encephalitis, aseptic meningitis, pulmonary edema, and acute flaccid paralysis. We identified new benzimidazole derivatives and described their in vitro cytotoxicity and broad-spectrum anti-enterovirus activity. Among them, derivative 2b resulted in interesting activity against EV-A71, and therefore it was selected for further investigations. Compound 2b proved to be able to protect cell monolayers from EV-A71-induced cytopathogenicity, with an EC50 of 3 µM. Moreover, Vero-76 cells resulted in being significantly protected from necrosis and apoptosis when treated with 2b at 20 and 80 µM. Compound 2b reduced viral adsorption to Vero-76 cells, and when evaluated in a time-of-addition assay, the derivative had the highest effect when added during the infection period. Moreover, derivative 2b reduced viral penetration into host cells. Besides, 2b did not affect intestinal monolayers permeability, showing no toxic effects. A detailed insight into the efficacy of compound 2b against EV-A71 showed a dose-dependent reduction in the viral titer, also at low concentrations. Mechanism of action investigations suggested that our derivative can inhibit viral endocytosis by reducing viral attachment to and penetration into host cells. Pharmacokinetic and toxicity predictions validated compound 2b as a good candidate for further in vivo assays.


Assuntos
Antivirais/farmacologia , Apoptose/efeitos dos fármacos , Benzimidazóis/farmacologia , Enterovirus Humano A/efeitos dos fármacos , Animais , Células CACO-2 , Chlorocebus aethiops , Doença de Mão, Pé e Boca/virologia , Células HeLa , Humanos , Células Vero , Carga Viral , Ensaio de Placa Viral
6.
Nat Prod Res ; 35(4): 633-636, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30908090

RESUMO

Nerium oleander (NO), a member of the Apocynaceae family, is an ornamental plant. In this study, we evaluated the antiviral activity of hot and cold extract of NO against six different viruses such as herpes simplex virus type 1 (HSV-1), polio virus type 1 (Sb-1), vesicular stomatitis virus (VSV), reovirus type-1 (Reo-1), human immunodeficiency virus type-1 (HIV-1), and yellow fever virus (YFV). Interestingly the results of plaque reduction assay demonstrated that both, hot extract and cold extract (breastin) of NO inhibited Sb-1 viral infection.In order to identify the mechanism by which NO exerts its antiviral activity, the virucidal effect, the time of addition and the adsorption assay were carried out. Results demonstrated that NO exerts its effect after infection period, particularly during the first two hours post infection.


Assuntos
Antivirais/farmacologia , Nerium/química , Extratos Vegetais/farmacologia , Poliovirus/efeitos dos fármacos , Animais , Morte Celular/efeitos dos fármacos , Chlorocebus aethiops , Cinética , Poliovirus/crescimento & desenvolvimento , Células Vero
7.
Nat Prod Res ; 35(24): 5674-5680, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32975126

RESUMO

In the prevention of epidemic and pandemic emerging and neglected viral infections, natural products are an important source of lead compounds. Hornstedtia bella Skornickis is a rhizomatous herb growing in the forest of central Vietnam. Hornstedtia bella essential oil (Hb EO) was recently characterised by our group as endowed of antimicrobial activity against Staphylococcus aureus Methicillin-Resistant strains. Here, we describe for the first time the evaluation of Hb EO against a spectrum of viruses responsible for important human diseases. Hb EO resulted active against Vaccinia virus (VV) (EC50 values 80 µg/mL), closely related to variola virus, causative agent of smallpox. Hb EO was able to strongly reduce the viral VV titer in cell-based assay at not cytotoxic concentration and its potential mode of action was characterised by virucidal activity evaluation followed by time-of-addition assay. Furthermore, Hb EO antiviral activity was implemented in a combination study with the mycophenolic acid.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Óleos Voláteis , Zingiberaceae , Antivirais/farmacologia , Humanos , Óleos Voláteis/farmacologia , Vaccinia virus
8.
Viruses ; 12(6)2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32575585

RESUMO

Historically, natural products have been the most successful source of inspiration for the development of new drugs. Members of the Thymelaeaceae family have been of interest owing to their excellent medicinal value. Given the successful history of natural product-based drug discovery, extracts from the aerial parts of Thymelaea hirsuta were essvaluated for their potential anti-human immunodeficiency virus type 1 (HIV-1) activity. Ethyl acetate extracts from leaves (71B) and branches (72B) of Thymelaea hirsuta showed potent and selective activity against HIV-1 wt (EC50 = 0.8 µg/mL) at non-cytotoxic concentrations (CC50 > 100 µg/mL). They proved to be active against HIV-1 variants carrying clinically relevant NNRTI and NRTI mutations at low concentration (0.3-4 µg/mL range) and against the M-tropic strain HIV-1 BaL. The 72B extract, chosen as a lead, was not able to inhibit the RT and protease enzymatic functions. Furthermore, it was not virucidal, since exposure of HIV to high concentration did not affect virus infectivity. The pre-clinical safety profile of this extract showed no adverse effect on the growth of Lactobacilli, and non-toxic concentration of the extract did not influence the Caco-2 epithelial cells monolayer integrity. Additionally, extract 72B prevented syncytia formation at low concentration (0.4 µg/mL). The potent inhibitory effect on the syncytia formation in co-cultures showed that 72B inhibits an early event in the replication cycle of HIV. All of these findings prompt us to carry on new studies on Thymelaea hirsuta extracts.


Assuntos
Fármacos Anti-HIV/farmacologia , Descoberta de Drogas/métodos , Infecções por HIV/tratamento farmacológico , Extratos Vegetais/farmacologia , Thymelaeaceae/química , Animais , Células CACO-2 , Bovinos , Linhagem Celular Tumoral , Chlorocebus aethiops , Cricetinae , HIV-1/efeitos dos fármacos , Humanos , Folhas de Planta/química , Células Vero
9.
Antibiotics (Basel) ; 9(6)2020 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-32570731

RESUMO

The rapid emergence of drug-resistant strains and novel viruses have motivated the search for new anti-infectious agents. In this study, the chemical compositions and cytotoxicity, as well as the antibacterial, antifungal, antitrichomonas, and antiviral activities of essential oils from the leaves, rhizomes, and whole plant of Hornstedtia bella were investigated. The GC/MS analysis showed that ß-pinene, E-ß-caryophyllene, and α-humulene were found at high concentrations in the essential oils. The essential oils exhibited (i) inhibition against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis with minimum inhibitory concentrations (MIC) and minimum lethal concentration (MLC) values from 1 to 4% (v/v); (ii) MIC and MLC values from 2 to 16% (v/v) in Candida tropicalis and Candida parapsilosis; (iii) MIC and MLC values from 4 to 16% in Enterococcus faecalis; and (iv) MIC and MLC values from 8 to greater than or equal to 16% (v/v) in the remaining strains, including Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Candida albicans, and Candida glabrata. In antitrichomonas activity, the leaves and whole-plant oils of Hornstedtia bella possessed IC50, IC90, and MLC values of 0.008%, 0.016%, and 0.03% (v/v), respectively, whilst those of rhizomes oil had in turn, 0.004%, 0.008%, and 0.016% (v/v).Besides, the leaf oil showed a weak cytotoxicity against Vero 76 and MRC-5; meanwhile, rhizomes and whole-plant oils did not exert any toxic effects on cell monolayers. Finally, these oils were not active against EV-A71.

10.
Plants (Basel) ; 9(4)2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32260297

RESUMO

:The present study aimed to determine the antimicrobial activity and chemical composition of leaves-extracted essential oil of Leoheo domatiophorus Chaowasku, D.T. Ngo and H.T. Le (L. domatiophorus), including antibacterial, antimycotic, antitrichomonas and antiviral effects. The essential oil was obtained using hydrodistillation, with an average yield of 0.34 ± 0.01% (v/w, dry leaves). There were 52 constituents as identified by GC/MS with available authentic standards, representing 96.74% of the entire leaves oil. The essential oil was comprised of three main components, namely viridiflorene (16.47%), (-)-δ-cadinene(15.58%) and γ-muurolene (8.00%). The oil showed good antimicrobial activities against several species: Gram-positive strains: Staphylococcus aureus (two strains) and Enterococcus faecalis, with Minimum Inhibitory Concentration (MIC) and Minimum Lethal Concentration (MLC) values from 0.25 to 1% (v/v); Gram-negative strains such as Escherichia coli (two strains), Pseudomonas aeruginosa (two strains) and Klebsiella pneumoniae, with MIC and MLC values between 2% and 8% (v/v); and finally Candida species, having MIC and MLC between 0.12 and 4% (v/v).Antitrichomonas activity of the oil was also undertaken, showing IC50, IC90 and MLC values of 0.008%, 0.016% and 0.03% (v/v), respectively, after 48h of incubation. The essential oil resultedin being completely ineffective against tested viruses, ssRNA+ (HIV-1, YFV, BVDV, Sb-1, CV-B4), ssRNA- (hRSVA2, VSV), dsRNA (Reo-1), and dsDNA (HSV-1, VV) viruses with EC50 values over 100 µg/mL. This is the first, yet comprehensive, scientific report about the chemical composition and pharmacological properties of the essential oil in L. domatiophorus.

11.
Viruses ; 12(1)2020 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-31968537

RESUMO

Orthohantaviruses, previously known as hantaviruses (family Hantaviridae, order Bunyavirales), are emerging zoonoses hosted by different rodent and insectivore species. Orthohantaviruses are transmitted by aerosolized excreta (urine, saliva and feces) of their reservoir hosts. When transmitted to humans, they cause hemorrhagic fever with renal syndrome (HFRS) in Asia and Europe and hantavirus (cardio) pulmonary syndrome (HPS) in the Americas. Clinical studies have shown that early treatments of HFRS patients with ribavirin (RBV) improve prognosis. Nevertheless, there is the need for urgent development of specific antiviral drugs. In the search for new RNA virus inhibitors, we recently identified a series of variously substituted 5,6-dichloro-1(2)-phenyl-1(2)H-benzo[d][1,2,3]triazole derivatives active against the human respiratory syncytial virus (HRSV). Interestingly, several 2-phenyl-benzotriazoles resulted in fairly potent inhibitors of the Hantaan virus in a chemiluminescence focus reduction assay (C-FRA) showing an EC50 = 4-5 µM, ten-fold more active than ribavirin. Currently, there are no FDA approved drugs for the treatment of orthohantavirus infections. Antiviral activities and cytotoxicity profiles suggest that 5,6-dichloro-1(2)-phenyl-1(2)H-benzo[d][1,2,3]triazoles could be promising candidates for further investigation as a potential treatment of hantaviral diseases.


Assuntos
Antivirais/farmacologia , Orthohantavírus/efeitos dos fármacos , Triazóis/química , Triazóis/farmacologia , Animais , Antivirais/química , Chlorocebus aethiops , Descoberta de Drogas , Células Vero
12.
Med Chem ; 16(5): 677-688, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31878859

RESUMO

BACKGROUND: Coxsackievirus infections are associated with cases of aseptic meningitis, encephalitis, myocarditis, and some chronic disease. METHODS: A series of benzo[d][1,2,3]triazol-1(2)-yl derivatives (here named benzotriazol-1(2)-yl) (4a-i, 5a-h, 6a-e, g, i, j and 7a-f, h-j) were designed, synthesized and in vitro evaluated for cytotoxicity and antiviral activity against two important human enteroviruses (HEVs) members of the Picornaviridae family [Coxsackievirus B 5 (CVB-5) and Poliovirus 1 (Sb-1)]. RESULTS: Compounds 4c (CC50 >100 µM; EC50 = 9 µM), 5g (CC50 >100 µM; EC50 = 8 µM), and 6a (CC50 >100 µM; EC50 = 10 µM) were found active against CVB-5. With the aim of evaluating the selectivity of action of this class of compounds, a wide spectrum of RNA (positive- and negativesense), double-stranded (dsRNA) or DNA viruses were also assayed. For none of them, significant antiviral activity was determined. CONCLUSION: These results point towards a selective activity against CVB-5, an important human pathogen that causes both acute and chronic diseases in infants, young children, and immunocompromised patients.


Assuntos
Antivirais/farmacologia , Enterovirus Humano B/efeitos dos fármacos , Poliovirus/efeitos dos fármacos , Ureia/farmacologia , Animais , Antivirais/síntese química , Antivirais/química , Chlorocebus aethiops , Testes de Sensibilidade Microbiana , Estrutura Molecular , Ureia/análogos & derivados , Ureia/química , Células Vero
13.
Front Chem ; 7: 247, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31041309

RESUMO

Human Respiratory Syncytial Virus (RSV) is the primary cause of bronchopneumonia in infants and children worldwide. Clinical studies have shown that early treatments of RSV patients with ribavirin improve prognosis, even if the use of this drug is limited due to myelosuppression and toxicity effects. Furthermore, effective vaccines to prevent RSV infection are currently unavailable. Thus, the development of highly effective and specific antiviral drugs for pre-exposure prophylaxis and/or treatment of RSV infections is a compelling need. In the quest of new RSV inhibitors, in this work we evaluated the antiviral activity of a series of variously substituted 5,6-dichloro-1-phenyl-1(2)H-benzo[d][1,2,3]triazole derivatives in cell-based assays. Several 1- and 2-phenyl-benzotriazoles resulted fairly potent (µM concentrations) inhibitors of RSV infection in plaque reduction assays, accompanied by low cytotoxicity in human highly dividing T lymphoid-derived cells and primary cell lines. Contextually, no inhibitory effects were observed against other RNA or DNA viruses assayed, suggesting specific activity against RSV. Further results revealed that the lead compound 10d was active during the early phase of the RSV infection cycle. To understand whether 10d interfered with virus attachment to target cells or virus-cell fusion events, inhibitory activity tests against the RSV mutant strain B1 cp-52-expressing only the F envelope glycoprotein-and a plasmid-based reporter assay that quantifies the bioactivity of viral entry were also performed. The overall biological results, in conjunction with in silico modeling studies, supported the conclusion that the RSV fusion process could be the target of this new series of compounds.

14.
ACS Infect Dis ; 5(4): 582-591, 2019 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-30816690

RESUMO

The fusion between the viral and the target cell membrane is a crucial step in the life cycle of enveloped viruses. The blocking of this process is a well-known therapeutic approach that led to the development of the fusion inhibitor peptide enfuvirtide, clinically used against human immunodeficiency virus (HIV) type 1. Despite this significant advance on viral treatment, the appearance of resistance has limited its clinical use. Such a limitation has led to the development of other fusion inhibitor peptides, such as C34, that present the same structural domain as enfuvirtide (heptad repeat sequence) but have different functional domains (pocket-binding domain in the case of C34 and lipid-binding domain in the case of enfuvirtide). Recently, the antiviral properties of 25-hydroxycholesterol were demonstrated, which boosted the interest in this oxysterol. The combination of two distinct antiviral molecules, C34 and 25-hydroxycholesterol, may help to suppress the emergence of resistant viruses. In this work, we characterized the interaction of the C34-25-hydroxycholesterol conjugate with biomembrane model systems and human blood cells. Lipid vesicles and monolayers with defined lipid compositions were used as biomembrane model systems. The conjugate interacts preferentially with membranes rich in sphingomyelin (a lipid enriched in lipid rafts) and presents a poor partition to membranes composed solely of phosphatidylcholine and cholesterol. We hypothesize that cholesterol causes a repulsive effect that is overcome in the presence of sphingomyelin. Importantly, the peptide shows a preference for human peripheral blood mononuclear cells relative to erythrocytes, which shows its potential to target CD4+ cells. Antiviral activity results against different wild-type and drug-resistant HIV strains further demonstrated the potential of C34-HC as a good candidate for future studies.


Assuntos
Inibidores da Fusão de HIV/farmacologia , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Hidroxicolesteróis/farmacologia , Peptídeos/farmacologia , Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Membrana Celular/química , Membrana Celular/metabolismo , Membrana Celular/virologia , Eritrócitos/química , Eritrócitos/metabolismo , Eritrócitos/virologia , Inibidores da Fusão de HIV/química , Infecções por HIV/sangue , Infecções por HIV/metabolismo , HIV-1/fisiologia , Humanos , Hidroxicolesteróis/química , Leucócitos Mononucleares/química , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/virologia , Peptídeos/química
15.
J Virol ; 93(8)2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30728259

RESUMO

A clinical isolate of measles virus (MeV) bearing a single amino acid alteration in the viral fusion protein (F; L454W) was previously identified in two patients with lethal sequelae of MeV central nervous system (CNS) infection. The mutation dysregulated the viral fusion machinery so that the mutated F protein mediated cell fusion in the absence of known MeV cellular receptors. While this virus could feasibly have arisen via intrahost evolution of the wild-type (wt) virus, it was recently shown that the same mutation emerged under the selective pressure of small-molecule antiviral treatment. Under these conditions, a potentially neuropathogenic variant emerged outside the CNS. While CNS adaptation of MeV was thought to generate viruses that are less fit for interhost spread, we show that two animal models can be readily infected with CNS-adapted MeV via the respiratory route. Despite bearing a fusion protein that is less stable at 37°C than the wt MeV F, this virus infects and replicates in cotton rat lung tissue more efficiently than the wt virus and is lethal in a suckling mouse model of MeV encephalitis even with a lower inoculum. Thus, either during lethal MeV CNS infection or during antiviral treatment in vitro, neuropathogenic MeV can emerge, can infect new hosts via the respiratory route, and is more pathogenic (at least in these animal models) than wt MeV.IMPORTANCE Measles virus (MeV) infection can be severe in immunocompromised individuals and lead to complications, including measles inclusion body encephalitis (MIBE). In some cases, MeV persistence and subacute sclerosing panencephalitis (SSPE) occur even in the face of an intact immune response. While they are relatively rare complications of MeV infection, MIBE and SSPE are lethal. This work addresses the hypothesis that despite a dysregulated viral fusion complex, central nervous system (CNS)-adapted measles virus can spread outside the CNS within an infected host.


Assuntos
Sistema Nervoso Central/virologia , Encefalite Viral , Corpos de Inclusão Viral , Pulmão/virologia , Vírus do Sarampo/fisiologia , Sarampo , Mutação de Sentido Incorreto , Proteínas Virais de Fusão , Replicação Viral , Substituição de Aminoácidos , Animais , Sistema Nervoso Central/metabolismo , Chlorocebus aethiops , Modelos Animais de Doenças , Encefalite Viral/genética , Encefalite Viral/metabolismo , Encefalite Viral/transmissão , Humanos , Corpos de Inclusão Viral/genética , Corpos de Inclusão Viral/metabolismo , Pulmão/metabolismo , Sarampo/metabolismo , Sarampo/transmissão , Camundongos , Camundongos Transgênicos , Sigmodontinae , Células Vero , Proteínas Virais de Fusão/genética , Proteínas Virais de Fusão/metabolismo
16.
Molecules ; 23(10)2018 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-30301264

RESUMO

A series of 2-(1H-indol-3-yl)ethylthiourea derivatives were prepared by condensation of 2-(1H-indol-3-yl)ethanamine with appropriate aryl/alkylisothiocyanates in anhydrous media. The structures of the newly synthesized compounds were confirmed by spectroscopic analysis and the molecular structures of 8 and 28 were confirmed by X-ray crystallography. All obtained compounds were tested for antimicrobial activity against Gram-positive cocci, Gram-negative rods and for antifungal activity. Microbiological evaluation was carried out over 20 standard strains and 30 hospital strains. Compound 6 showed significant inhibition against Gram-positive cocci and had inhibitory effect on the S. aureus topoisomerase IV decatenation activity and S. aureus DNA gyrase supercoiling activity. Compounds were tested for cytotoxicity and antiviral activity against a large panel of DNA and RNA viruses, including HIV-1 and other several important human pathogens. Interestingly, derivative 8 showed potent activity against HIV-1 wild type and variants bearing clinically relevant mutations. Newly synthesized tryptamine derivatives showed also a wide spectrum activity, proving to be active against positive- and negative-sense RNA viruses.


Assuntos
Indóis/síntese química , Staphylococcus aureus/efeitos dos fármacos , Tioureia/síntese química , Inibidores da Topoisomerase II/síntese química , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Cristalografia por Raios X , DNA Girase/efeitos dos fármacos , DNA Topoisomerase IV/antagonistas & inibidores , Humanos , Indóis/química , Indóis/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Staphylococcus aureus/enzimologia , Staphylococcus aureus/patogenicidade , Tioureia/química , Tioureia/farmacologia , Inibidores da Topoisomerase II/química , Inibidores da Topoisomerase II/farmacologia
17.
Molecules ; 23(10)2018 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-30248936

RESUMO

4-Chloro-3-nitrophenylthioureas 1⁻30 were synthesized and tested for their antimicrobial and cytotoxic activities. Compounds exhibited high to moderate antistaphylococcal activity against both standard and clinical strains (MIC values 2⁻64 µg/mL). Among them derivatives with electron-donating alkyl substituents at the phenyl ring were the most promising. Moreover, compounds 1⁻6 and 8⁻19 were cytotoxic against MT-4 cells and various other cell lines derived from human hematological tumors (CC50 ≤ 10 µM). The influence of derivatives 11, 13 and 25 on viability, mortality and the growth rate of immortalized human keratinocytes (HaCaT) was observed.


Assuntos
Antibacterianos/farmacologia , Queratinócitos/citologia , Feniltioureia/análogos & derivados , Antibacterianos/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Humanos , Queratinócitos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Staphylococcus/efeitos dos fármacos , Testes de Toxicidade
18.
Eur J Med Chem ; 145: 559-569, 2018 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-29339251

RESUMO

Enteroviruses are among the most common and important human pathogens for which there are no specific antiviral agents approved by the US Food and Drug Administration so far. Particularly, coxsackievirus infections have a worldwide distribution and can cause many important diseases. We here report the synthesis of new 14 quinoxaline derivatives and the evaluation of their cytotoxicity and antiviral activity against representatives of ssRNA, dsRNA and dsDNA viruses. Promisingly, three compounds showed a very potent and selective antiviral activity against coxsackievirus B5, with EC50 in the sub-micromolar range (0.3-0.06 µM). A combination of experimental techniques (i.e. virucidal activity, time of drug addition and adsorption assays) and in silico modeling studies were further performed, aiming to understand the mode of action of the most active, selective and not cytotoxic compound, the ethyl 4-[(2,3-dimethoxyquinoxalin-6-yl)methylthio]benzoate (6).


Assuntos
Antivirais/farmacologia , Enterovirus Humano B/efeitos dos fármacos , Quinoxalinas/farmacologia , Animais , Antivirais/síntese química , Antivirais/química , Bovinos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cricetinae , Relação Dose-Resposta a Droga , Haplorrinos , Humanos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Quinoxalinas/síntese química , Quinoxalinas/química , Relação Estrutura-Atividade
19.
RSC Adv ; 8(57): 32651-32658, 2018 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-35547702

RESUMO

The high worldwide demand for amorphous precipitated silica (APS) materials, millions of tons worth billions of dollars, makes it worthwhile to further expand the techniques for synthesizing new, cheap, and environmentally friendly resources. In this research, amorphous precipitated silica was synthesized from alkaline dissolution of olivine using a mixture of NaOH and KOH and characterized; this combination resulted in better kinetics than those of the separate components. Experimental parameters (concentration of alkali, liquid/solid ratio, reaction time, and temperature) were optimized to provide maximum recovery of APS from olivine dissolution, which was then characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Brunauer-Emmett-Teller (BET) N2 adsorption-desorption measurements, and thermogravimetric analysis (TGA). The APS possessed suitable morphology for use as an additive in polymers and in catalysis: a particle size below 10 nm, pore width of 5.59 nm, BJH adsorption cumulative pore volume of 0.96 cm3 g-1, BET surface area of 670.8 m2 g-1, and Langmuir surface area of 859.3 m2 g-1. The apparent activation energy of olivine dissolution with a mixture of NaOH/KOH was 43.6 kJ mol-1. The steps involved in creation of APS from olivine resulted in opportunities for carbon dioxide absorption, which could contribute to the production of valuable materials through decarbonation of exhaust gases.

20.
RSC Adv ; 8(63): 36200, 2018 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-35560979

RESUMO

[This corrects the article DOI: 10.1039/C8RA06257A.].

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