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1.
Int J Mol Sci ; 22(14)2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34299238

RESUMO

This study focused on the biological evaluation and chemical characterization of Geranium pyrenaicum Burm. f. Different solvent extracts (hexane, ethyl acetate, methanol, and water extracts) were prepared. The phytochemical profile, antioxidant, and enzyme inhibitory activity were investigated. Cytotoxicity was assessed using VERO, FaDu, HeLa and RKO cells. The antiviral activity was carried out against HSV-1 (Herpes simplex virus 1) propagated in VERO cell line. The aqueous extract, possessing high phenolic content (170.50 mg gallic acid equivalent/g extract), showed the highest reducing capacity (613.27 and 364.10 mg Trolox equivalent/g extract, for cupric reducing antioxidant capacity and ferric reducing antioxidant power, respectively), radical scavenging potential (469.82 mg Trolox equivalent/g extract, against 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)), metal chelating ability (52.39 mg ethylenediaminetetraacetic acid equivalent/g extract) and total antioxidant capacity (3.15 mmol Trolox equivalent/g extract). Liquid chromatography-electrospray ionization-quadrupole time-of-flight-mass spectrometry (LC-ESI-QTOF-MS/MS) alloved to tentatively identify a total of 56 compounds in the extracts, including ellagitannins, gallic acid and galloyl derivatives amongst others. The ethyl acetate extracts substantially depressed cholinesterase enzymes (4.49 and 12.26 mg galantamine equivalent/g extract against AChE and BChE, respectively) and α-amylase enzyme (1.04 mmol acarbose equivalent/g extract). On the other hand, the methanolic extract inhibited tyrosinase (121.42 mg kojic acid equivalent/g extract) and α-glucosidase (2.39 mmol acarbose equivalent/g extract) activities. The highest selectivity towards all cancer cell lines (SI 4.5-10.8) was observed with aqueous extract with the FaDu cells being the most sensitive (CC50 40.22 µg/mL). It can be concluded that the presence of certain bioactive antiviral molecules may be related to the high anti HSV-1 activity of the methanolic extract. This work has generated vital scientific data on this medicinal plant, which is a prospective candidate for the creation of innovative phyto-pharmaceuticals.


Assuntos
Geranium/metabolismo , Extratos Vegetais/química , Animais , Antioxidantes , Antivirais , Linhagem Celular , Cromatografia Líquida de Alta Pressão/métodos , Flavonoides/análise , Humanos , Fenóis/análise , Compostos Fitoquímicos/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Estudos Prospectivos , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos
2.
Sci Rep ; 11(1): 10654, 2021 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-34017038

RESUMO

The purpose of this study was to determine if a methanolic extract of the Pulsatilla patens (L.) Mill. can inhibit the progression of cancer through the modulation of cancer-related metabolic signaling pathways. We analyzed a panel of 13 inducible luciferase reporter gene vectors which expression is driven by enhancer elements that bind to specific transcription factors for the evaluation of the activity of cancer signaling pathways. The root extract of P. patens exhibited strong inhibition of several signaling pathways in HeLa cells, a cervical cancer cell line, and was found to be the most potent in inhibiting the activation of Stat3, Smad, AP-1, NF-κB, MYC, Ets, Wnt and Hdghog, at a concentration of 40 µg/mL. The methanolic extracts of P. patens enhanced apoptotic death, deregulated cellular proliferation, differentiation, and progression towards the neoplastic phenotype by altering key signaling molecules required for cell cycle progression. This is the first study to report the influence of Pulsatilla species on cancer signaling pathways. Further, our detailed phytochemical analysis of the methanolic extracts of the P. patens allowed to deduce that compounds, which strongly suppressed the growth and proliferation of HeLa cancer cells were mainly triterpenoid saponins accompanied by phenolic acids.


Assuntos
Neoplasias/metabolismo , Extratos Vegetais/farmacologia , Pulsatilla/química , Transdução de Sinais , Morte Celular/efeitos dos fármacos , Ácidos Cumáricos/farmacologia , Genes Reporter , Células HeLa , Humanos , Limite de Detecção , Luciferases/metabolismo , Metanol , Proteínas de Neoplasias/metabolismo , Neoplasias/patologia , Raízes de Plantas/química , Reprodutibilidade dos Testes , Saponinas/química , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Triterpenos/química , Triterpenos/farmacologia
3.
J Pharm Biomed Anal ; 198: 114018, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33730614

RESUMO

Caesalpinia bonduc and C. decapeleta var. japonica have great importance in traditional medicine systems but scientific information's are still lacking for their potentials. To explore their bioactivity, we assessed the antioxidant, enzyme inhibitory abilities of the dichloromethane (DCM), ethyl acetate, methanol, and water extracts prepared from the leaves and bark. The cytotoxicity and anticancer properties of the extracts were also assessed in vitro. The water extract of C. decapeleta leaves possessed highest phenolic content (108.16 mg gallic acid equivalent (GAE)/g extract), while the highest flavonoid content was recorded for the C. bonduc leaf methanolic extract (27.89 mg rutin equivalent (RE)/g extract). In general, C. decapeleta extracts possessed higher radical scavenging potential compared to C. bonduc extracts. C. decapeleta DCM leaves extract (10.20 mg galantamine equivalent (GALAE)/g extract) showed highest inhibition against butyrylcholinesterase. The cytotoxicity of the most potent methanolic and aqueous extracts were assessed against four cell lines. The chemical profiles of both species appeared to be different. C. bonduc was abundant in organic and phenolic acids as well as their esters. Flavonoid glycosides, bonducellin and its derivatives and caesalminaxins were identified. Whereas, C. decalpetala possessed many galloylated compounds. The cytotoxicity of C. bonduc and C. decapetala extracts was tested using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) based assay on VERO (kidney of an adult African Green monkey cells), HeLa (human cervical adenocarcinoma cells), RKO (human colon carcinoma cells), FaDu (human hypopharyngeal squamous carcinoma cells) cell lines. C. bonduc bark water extract exhibited the highest cytotoxicity towards HeLa (50 % cytotoxic concentration (CC50): 28.5 µg/mL) cancer cell line, as compared to normal VERO cells (CC50:35.87 µg/mL). For C. decapetala, the highest cytotoxicity was found for bark methanol extract on the HeLa cells with CC50 of 46.08 µg/mL and selectivity index of 3.33. In the gene ontology analysis, prostate cancer, nuclear factor kappa B (NF-kappa B) signaling, proteoglycans in cancer pathways might support the results of the cytotoxic assays. These results showed that the tested Caesalpinia species, showing potent inhibitory action against butyrylcholinesterase, might represent novel phytotherapeutic avenues for the management of Alzheimer's disease.


Assuntos
Farmácia , Extratos Vegetais , Animais , Antioxidantes/farmacologia , Chlorocebus aethiops , Biologia Computacional , Células HeLa , Humanos , Extratos Vegetais/farmacologia , Células Vero
4.
Foods ; 9(6)2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32492817

RESUMO

Fibigia clypeata (L.) Medik. is a poorly studied plant species belonging to the Brassicaceae family, and usually used as cress in the salads. The current investigation aimed at assessing the antioxidant potential and inhibitory activity of ethyl acetate, methanol, and aqueous extracts of F. clypeata against key enzymes targeted in the management of type II diabetes (α-amylase and α-glucosidase), Alzheimer's disease (acetylcholinesterase and butyrylcholinesterase), and skin hyperpigmentation (tyrosinase). Cytotoxicity of the extracts was also determined using normal VERO and cancer FaDu and SCC-25 cell lines. Besides, LC-MS was employed to investigate the detailed phytochemical profiles of the extracts. The methanol extract showed potent enzyme inhibitory activity (4.87 mg galantamine equivalent/g, 3.52 mg galantamine equivalent/g, 126.80 mg kojic acid equivalent/g, and 24.68 mg acarbose equivalent/g, for acetylcholinesterase, butyrylcholinesterase, tyrosinase, and α-glucosidase, respectively) and antioxidant potential (96.52, 109.10, 154.02, and 104.85 mg trolox equivalent/g, for DPPH, ABTS, CUPRAC, and FRAP assays, respectively). Interestingly, caffeic acid-O-hexoside derivative, caffeyl alcohol O-glucopyranoside, and ferulic acid derivative were identified in all extracts. F. clypeata extracts showed no cytotoxicity towards VERO cell line and a weak cytotoxic potential against FaDu and SCC-25 cell lines. Interesting scientific evidence gathered from the present study support further investigation on F. clypeata in the view of designing and developing a novel therapeutic agent for the management of Alzheimer's disease, type II diabetes, skin hyperpigmentation problems, as well as cancer.

5.
Oxid Med Cell Longev ; 2019: 5832410, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31360295

RESUMO

A growing number of studies reveal that oxidative stress is associated with viral infections or cancer development. However, there are few reports assessing the relationships between oxidative stress, viral infection, and carcinogenesis. The present study analyzed the level of total antioxidant status (TAS) as well as the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) in patients with oropharyngeal cancer both Epstein-Barr virus (EBV)-positive and EBV-negative in comparison with the control group. The correlations between these parameters and EBV type (wild-type LMP1 (wt-LMP1) or LMP1 with deletion (del-LMP1)), level of antibodies against EBV, the degree of tumor differentiation, and TNM classification were also investigated. Fresh frozen tumor tissue samples collected from 66 patients with oropharyngeal squamous cell carcinoma were tested using nested PCR assay for EBV DNA detection. Spectrophotometric methods were used to measure TAS values as well as SOD and GPx activities in homogenates of tissue, using diagnostic kits produced by Randox Laboratories. Sera from all individuals were investigated using ELISA method to detect the presence of Epstein-Barr virus capsid antigen (EBVCA) IgM and IgG, Epstein-Barr virus nuclear antigen (EBNA) IgG, and early antigen (EA) IgG antibodies. The level of TAS and activities of antioxidant enzymes (GPx and SOD) were significantly decreased in tissues with oropharyngeal cancer, particularly in EBV-positive cases. In 82.3% of patients, wt-LMP1 was detected. Significantly lower TAS, GPx, and SOD values were stated in patients infected with wild-type EBV. The presence of antibodies against early antigen (anti-EA) was detected in over 80% of patients, which suggests reactivation of EBV infection. The correlation between the degree of tumor differentiation and TN classification, especially in EBV-positive patients, was also observed. Determination of these parameters may be useful in evaluating tumor burden in patients with various stages of oropharyngeal cancer and could be an important prognostic factor. Future studies are needed to understand the role of EBV lytic reactivation induced by oxidative stress.


Assuntos
Antioxidantes/química , Infecções por Vírus Epstein-Barr/diagnóstico , Glutationa Peroxidase/metabolismo , Herpesvirus Humano 4/isolamento & purificação , Neoplasias Orofaríngeas/diagnóstico , Superóxido Dismutase/metabolismo , Idoso , Anticorpos Antivirais/sangue , Antioxidantes/metabolismo , DNA Viral/metabolismo , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/metabolismo , Feminino , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/complicações , Neoplasias Orofaríngeas/metabolismo
6.
Food Chem Toxicol ; 129: 115-124, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31029723

RESUMO

Essential oils (EO) possess a wide range of biological activities. However, their application in aqueous media is often limited due to their hydrophobicity and volatile character. This study was designed to prepare stable, water-dilutable microemulsions (ME) containing essential oils of citronella (Cymbopogon nardus (L.) Rendle), mint (Mentha x piperita L. 'Multimentha') and eucalyptus (Eucalyptus globulus Labill.) and to evaluate their in vitro antioxidant and cytotoxic properties. The comparison of cytotoxicity of EO solubilised in microemulsions and in dimethyl sulfoxide as well as the recovery of volatiles from cells culture medium over time was also performed. The clear ME were obtained in a range between 10% and 50% of aqueous phase for citronella EO and up to 60% of aqueous phase for mint and eucalyptus EO, in all ratios of Tween 80 to oil phase (from 5:1 to 9:1). Microemulsions of EO (EO/ME) showed higher antioxidant activity compared to EO. The increase in activity was 13.96%, 22.25% and 45.60% for eucalyptus, mint and citronella EO, respectively. The analysis of cytotoxicity profiles of EO/ME and EO/DMSO in Vero and HeLa cell lines showed differences in activity, however, they were statistically significant only in case of mint EO. Furthermore, it can be concluded that after 24 h of incubation ME vehicle itself was responsible for the observed cytotoxic effect. At the same time ME provided good solubility of constituents of EO and diminished evaporation of volatiles from culture medium.


Assuntos
Antioxidantes/química , Emulsões , Óleos Voláteis/química , Animais , Chlorocebus aethiops , Meios de Cultura , Células HeLa , Humanos , Solubilidade , Células Vero
7.
Eur J Pharm Sci ; 132: 34-43, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-30807815

RESUMO

The present study was aimed at broadening the profile of toxicity and biological activity of promising fused azaisocytosine-containing congeners (I-VI) possessing medical applicability and important pharmacokinetic properties. For this purpose, the in vivo zebrafish test was applied for evaluating embryotoxic effects of test compounds, whereas the ex vivo model of oxidatively-stressed rat erythrocytes was developed for assessing their antihaemolytic activities. Additionally, the MTT-based assays suitable for assessing cytotoxic and antiviral activities of I-VI were employed. The influence of compounds I-VI on zebrafish embryos/larvae was carefully investigated in relation to lack or presence of various substituents at the phenyl moiety. The least embryotoxic proved to be the parent compound (I) and its para-methyl (II) and ortho-chloro (III) derivatives. Simultaneously, they revealed the minimum embryotoxic concentrations higher than that of aciclovir, what makes them safer than this pharmaceutic. Moreover, most of test compounds showed protective effects (better or comparable to that of ascorbic acid) on oxidatively-stressed erythrocytes. All the investigated compounds were effective at inhibiting the growth of human solid tumours of pharynx (FaDu) and tongue (SCC-25). The majority of molecules showed good selectivity indices. The most selective proved to be II showing in normal Vero cells over a 5-fold and an almost 3-fold decreased cytotoxicity relative to that in tumour SCC-25 and FaDu cells, respectively. Additionally, a 3,4-dichloro derivative (VI) was shown to possess concentration-dependent inhibitory effects on the replication of Herpes simplex virus type 1 and simultaneously at active concentrations was found to be nontoxic for normal Vero cells.


Assuntos
Antineoplásicos/farmacologia , Antivirais/farmacologia , Compostos Aza/química , Citosina/análogos & derivados , Embrião não Mamífero/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Compostos Heterocíclicos de Anéis Fundidos/farmacologia , Peixe-Zebra , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/toxicidade , Antivirais/química , Antivirais/farmacocinética , Antivirais/toxicidade , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Citosina/química , Relação Dose-Resposta a Droga , Embrião não Mamífero/anormalidades , Eritrócitos/efeitos dos fármacos , Herpesvirus Humano 1/efeitos dos fármacos , Compostos Heterocíclicos de Anéis Fundidos/química , Compostos Heterocíclicos de Anéis Fundidos/farmacocinética , Compostos Heterocíclicos de Anéis Fundidos/toxicidade , Células Vero , Replicação Viral/efeitos dos fármacos , Peixe-Zebra/crescimento & desenvolvimento
8.
Anticancer Agents Med Chem ; 18(4): 529-540, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29065843

RESUMO

OBJECTIVE/METHOD: A group of 4-benzoyl-1-dichlorobenzoylthiosemicarbazides endowed with antibacterial activity was evaluated for its cytotoxic properties against breast cancer cells (MCF-7, MDA-MB-231) and head and neck squamous cell carcinomas (FaDu, SCC-25). Cytotoxicity of the investigated compounds was measured using MTT and [3H]-thymidine incorporation bioassays. RESULT: 1-(2,3-Dichlorobenzoyl)-4-(2-methylbenzoyl)thiosemicarbazide (TA-4), 1-(2,4-dichlorobenzoyl)- 4-(2-methylbenzoyl)thiosemicarbazide (TA-18), and 1-(2,4-dichlorobenzoyl)-4-(4-nitrolbenzoyl)- thiosemicarbazide (TA-20) were found to possess anticancer activity equipotent or even stronger than that of reference drug - etoposide. In order to clarify the molecular mode of action of the mentioned compounds, the relaxation assay kit for human DNA topoisomerase II was used. It turned out that reduction of viability of cancer cells was a result of inhibition of human DNA topoII. Molecular docking studies proved that 4-benzoyl-1-dichlorobenzoylthiosemicarbazides strongly interact with DNAdependent subunit of that enzyme.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Inibidores da Topoisomerase II/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , DNA Topoisomerases Tipo II/metabolismo , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Fibroblastos/efeitos dos fármacos , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade , Inibidores da Topoisomerase II/síntese química , Inibidores da Topoisomerase II/química
9.
Ann Agric Environ Med ; 24(3): 423-427, 2017 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-28954483

RESUMO

INTRODUCTION AND OBJECTIVE: Lithium is used in medicine but its application may cause diverse side effects. Selenium has been found to show protective properties against negative influence of different harmful factors. This study was aimed at evaluating the influence of non-toxic dose of lithium on antioxidant parameters in FaDu (ATCC HTB-43) and Vero (ECACC No. 84113001) cell lines as well as the possible protective effect of non-toxic concentration of sodium selenite. MATERIAL AND METHODS: The cells were subjected to 0.17 mmol/L of Li2CO3 and/or 2.9 µmol/L of Na2SeO3 · 5H2O for Vero as well as 0.47 mmol/L of Li2CO3 and/or 3.0 µmol/L of Na2SeO3 · 5H2O for FaDu cells. The incubation was continued for the subsequent 72 h. In the cells total antioxidant status (TAS) values, activities of antioxidant enzymes - superoxide dismutase (SOD) and glutathione peroxidase (GPx) as well as the reduced glutathione concentration (GSH) were determined. RESULTS AND CONCLUSION: In Vero cells lithium decreased all studied parameters, particularly GPx. Selenium co-treatment showed a distinct protective effect. In FaDu cells the similar effect was observed only in case of GSH. The results point to differences in action of lithium and selenium in physiological and pathological state. As long-term lithium therapy is applied in psychiatric patients the results regarding Vero line let suggest that selenium might be considered as an adjuvant alleviating side effects of Li-treatment.


Assuntos
Antioxidantes/metabolismo , Lítio/toxicidade , Oxidantes/toxicidade , Substâncias Protetoras/farmacologia , Selênio/farmacologia , Animais , Linhagem Celular , Chlorocebus aethiops , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Humanos , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Células Vero
10.
Food Chem Toxicol ; 109(Pt 2): 820-826, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28528251

RESUMO

A composition of essential oils obtained from Heracleum mantegazzianum (Apiaceae) was examined using a GC-MS method. n-Octyl acetate (19.92%), n-hexyl-2-methylbutanoate (10.84%), n-octanol (10.13%), n-octyl butanoate (8.88%), n-octyl-2-methylbutanoate (8.01%), n-hexyl acetate (7.11%), n-octyl isobutanoate (5.5%) and n-hexyl isobutanoate (5.43%) were the main compounds. The high-performance counter-current chromatography was applied for purification of aliphatic alcohols and esters. A mixture of n-hexane, acetonitrile and tetr-butyl methyl ether (1:1:0.1, v/v) allowed to obtain n-octanol, n-octyl acetate, n-hexyl-2- methylbutanoate, n-octyl isobutanoate and n-octyl-2-methylbutanoate, with the purity range of 94-99%, in one single 74 min run. The antimicrobial activity was also determined against plant and foodborne pathogens. While n-octanol shares responsibility for the antibacterial activity of the essential oil, n-octyl acetate determines its antifungal action. The cytotoxic activity assessed on two normal kidney fibroblast cell lines: Vero (animal) and HEK-293 (human embryonic), and two human cancer cell lines: FaDu (squamous cell carcinoma of the pharynx) and SCC25 (squamous cell carcinoma of the tongue), showed a moderate cytotoxicity with CC50 values ranging from 262.3 to 567.8 µg/mL. Results indicate that normal cell lines were more sensitive to the tested essential oil than cancer cell lines. The antioxidant activity of oil and pure compounds was not significant.


Assuntos
Anti-Infecciosos/farmacologia , Heracleum/química , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , 1-Octanol/química , 1-Octanol/isolamento & purificação , 1-Octanol/farmacologia , Acetatos/química , Acetatos/isolamento & purificação , Acetatos/farmacologia , Animais , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Bactérias/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Frutas/química , Fungos/efeitos dos fármacos , Cromatografia Gasosa-Espectrometria de Massas , Células HEK293 , Humanos , Testes de Sensibilidade Microbiana , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Células Vero
11.
Food Chem Toxicol ; 109(Pt 2): 1026-1031, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28487231

RESUMO

The dichloromethane extract from fruits of Angelica archangelica L. was separated by the modern high-performance countercurrent chromatography (HPCCC). The extract and five pure compounds: xanthotoxin, bergapten, imperatorin, phellopterin and isoimperatorin, and the mixture of imperatorin and phellopterin, have been studied as the potential antiviral agents against Herpes simplex virus type l and Coxsackievirus B3. The cytotoxicity was measured using the MTT method. Compounds were tested for the in vitro antiviral activity using the cytopathic effect (CPE) inhibitory assay and by the virus titre reduction assay. Real-time PCR was used to quantify the relative inhibition of the HSV-1 replication. The results indicate that the highest activity was demonstrated by the extract, imperatorin, phellopterin and the mixture of imperatorin and phellopterin, reducing the HSV-1 replication by 5.61 log, 4.7 log, 3.01 log and 3.73 log, respectively. The influence of isolated compounds on the CVB3 replication was not significant. Only the extract caused the decrease in the titre of virus in relation to the virus control. Our results show that coumarins of A. archangelica L. might be a potential candidate for the development of the alternative natural anti- HSV-1 compound. Moreover, the presence of isopentenyloxy moiety at C-8 position significantly improves their activity.


Assuntos
Angelica archangelica/química , Antivirais/química , Antivirais/farmacologia , Enterovirus Humano B/efeitos dos fármacos , Herpesvirus Humano 1/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Antivirais/isolamento & purificação , Distribuição Contracorrente , Infecções por Coxsackievirus/virologia , Enterovirus Humano B/fisiologia , Herpes Simples/virologia , Herpesvirus Humano 1/fisiologia , Humanos , Extratos Vegetais/isolamento & purificação , Replicação Viral/efeitos dos fármacos
12.
J Enzyme Inhib Med Chem ; 31(3): 361-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-25798689

RESUMO

Novel 1-(1,3-disubstituted-imidazolidyn-2-ylidene)-3-ethoxycarbonylmethylurea derivatives (3a-3j) were obtained from appropriate 1-aryl-3-arylsulfonyl-1H-imidazolidine-2-imines (1a-1j) and ethyl isocyanatoacetate (2), which were subjected to condensation. Seven compounds were tested for their antiviral activity against HSV-1 and CVB3 viruses. Among the tested compounds, 3c was found to be active against HSV-1, proving that 4-methoxy substituent as R and 4-methyl substituent as R1 are most beneficial for activity against this virus. Furthermore, 3e and 3g were active against CVB3, which demonstrated that both 4-methyl and 4-chloro substitution is tolerated as R1, whereas 4-chloro and 2-methoxy substituents are best as R. It was also shown that the active compounds are characterized by relatively big surface area, small ovality, and greatest HOMO and LUMO energies in comparison to the rest of the compounds.


Assuntos
Antivirais/síntese química , Antivirais/farmacologia , Enterovirus Humano B/efeitos dos fármacos , Herpesvirus Humano 1/efeitos dos fármacos , Compostos de Metilureia/farmacologia , Antivirais/química , Relação Dose-Resposta a Droga , Compostos de Metilureia/síntese química , Compostos de Metilureia/química , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade
13.
J Enzyme Inhib Med Chem ; 31(5): 787-95, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26212601

RESUMO

Novel 1-(1-aryl-4,5dihydro-1H-imidazoline)-3-chlorosulfonylourea derivatives 3a-3f were synthesized in the reaction of 1-aryl-4,5-dihydro-1H-imidazol-2-amines with chlorosulfonyl isocyanate. The second series of compounds 4a-4f was prepared from the respective 1-(1-aryl-4,5-dihydro-1H-imidazoline)-3-chlorsulfonylureas 3a-3f and 1,1'-carbonyldiimidazole (CDI). The selected compounds were tested for their activity against Herpes simplex virus and coxsackievirus B3 (CVB3). It was determined that three derivatives, i.e 3d, 4a and 4d are active against Herpes simplex virus (HSV-1). Compounds 3d and 4c are active against CVB3. Their favorable activity can be primarily attributed to their low lipophilicity values. Moreover, the lack of substituent in the phenyl moiety or 4-methoxy substitution can be considered as the most beneficial for the antiviral activity.


Assuntos
Antivirais/química , Antivirais/farmacologia , Enterovirus Humano B/efeitos dos fármacos , Simplexvirus/efeitos dos fármacos , Ureia/química , Ureia/farmacologia , Animais , Antivirais/síntese química , Chlorocebus aethiops , Infecções por Coxsackievirus/tratamento farmacológico , Ciclização , Herpes Simples/tratamento farmacológico , Imidazolinas/síntese química , Imidazolinas/química , Imidazolinas/farmacologia , Modelos Moleculares , Estrutura Molecular , Relação Estrutura-Atividade , Ácidos Sulfônicos/síntese química , Ácidos Sulfônicos/química , Ácidos Sulfônicos/farmacologia , Ureia/síntese química , Células Vero
14.
Eur J Med Chem ; 97: 94-103, 2015 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-25951434

RESUMO

A series of 1,2,4-triazole-based compounds was designed as potential antibacterial agents using molecular hybridization approach. The target compounds (23-44) were synthesized by Mannich reaction of 1,2,4-triazole-3-thione derivatives with ciprofloxacin (CPX) and formaldehyde. Their potent antibacterial effect on Gram-positive bacteria was accompanied by similarly strong activity against Gram-negative strains. The toxicity of the CPX-triazole hybrids for bacterial cells was even up to 18930 times higher than the toxicity for human cells. The results of enzymatic studies showed that the antibacterial activity of the CPX-triazole hybrids is not dependent solely on the degree of their affinity to DNA gyrase and topoisomerase IV.


Assuntos
Antibacterianos/síntese química , Ciprofloxacina/síntese química , Triazóis/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Ciprofloxacina/química , Ciprofloxacina/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Células HEK293 , Humanos , Concentração Inibidora 50 , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Triazóis/química , Triazóis/farmacologia
15.
Molecules ; 20(4): 6254-72, 2015 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-25859782

RESUMO

We have synthesized and examined the antibacterial activity, toxicity and affinity towards bacterial type II topoisomerases of a series of 1,2,4-triazole-ciprofloxacin hybrids. A number of these compounds displayed enhanced activity against Gram-positive and Gram-negative bacteria when compared to ciprofloxacin. The toxic concentrations of the obtained derivatives, evaluated on HEK-293 cells using MTT assay, were much higher than concentrations required to produce antibacterial effect. Finally, the results of enzymatic studies showed that the analyzed compounds demonstrated other preferences as regards primary and secondary molecular targets than ciprofloxacin.


Assuntos
Antibacterianos/farmacologia , Ciprofloxacina/farmacologia , Inibidores da Topoisomerase II/farmacologia , Triazóis/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Ciprofloxacina/síntese química , Ciprofloxacina/química , DNA Topoisomerases Tipo II/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Células HEK293 , Humanos , Relação Estrutura-Atividade , Inibidores da Topoisomerase II/síntese química , Inibidores da Topoisomerase II/química , Triazóis/síntese química , Triazóis/química
16.
Food Chem Toxicol ; 52: 188-92, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23182739

RESUMO

Mutellina purpurea is an aromatic Apiaceae plant known as Alpine lovage. Its polar extracts consist of phenolic acids, tannins and flavonoids. The cytotoxic effect of methanolic and aqueous extracts from M. purpurea was studied on the most frequently used cell lines: HeLa and BHK-21. Taking into account that the natural products are often used with other medicines there is a risk of reciprocal interaction on the metabolic level. Thus, the influence of M. purpurea extracts was investigated on the activity of CYP2D6 and CYP3A4, which are the most important P450 isoenzymes from the pharmacological and toxicological points of view. Additionally, because M. purpurea contains phenolic compounds, the antioxidative properties of this plant extracts were also studied and compared.


Assuntos
Antioxidantes/farmacologia , Apiaceae/química , Citocromo P-450 CYP2D6/metabolismo , Citocromo P-450 CYP3A/metabolismo , Extratos Vegetais/farmacologia , Animais , Benzotiazóis/metabolismo , Linhagem Celular , Cricetinae , Inibidores do Citocromo P-450 CYP2D6 , Inibidores do Citocromo P-450 CYP3A , Citotoxinas/farmacologia , Inibidores Enzimáticos/farmacologia , Células HeLa/efeitos dos fármacos , Humanos , Metanol/química , Extratos Vegetais/química , Ácidos Sulfônicos/metabolismo
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