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1.
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
2.
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.

3.
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
4.
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
5.
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
6.
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
7.
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
8.
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
9.
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
10.
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
11.
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
12.
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
13.
Med Chem Res ; 23: 1057-1066, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24465123

RESUMO

During this study, we have investigated in vitro activity of N-substituted-3-amino-5-oxo-4-phenyl-2,5-dihydro-1H-pyrazole-1-carbothioamide derivatives with N-ethyl, N-(4-metoxyphenyl) and N-cyclohexyl substituents against Gram-negative Haemophilus influenzae and H. parainfluenzae bacteria. A spectrophotometric assay was used in order to determine the bacterial growth and biofilm formation using a microtiter plate to estimate minimal inhibitory concentration (MIC) and minimal biofilm inhibitory concentration (MBIC). Among the tested N-substituted pyrazole derivatives, only N-ethyl-3-amino-5-oxo-4-phenyl-2,5-dihydro-1H-pyrazole-1-carbothioamide showed a significant in vitro activity against both planktonic cells of H. parainfluenzae (MIC = 0.49-31.25 µg ml-1) and H. influenzae (MIC = 0.24-31.25 µg ml-1) as well as biofilm-forming cells of H. parainfluenzae (MBIC = 0.24-31.25 µg ml-1) and H. influenzae (MBIC = 0.49 to ≥31.25 µg ml-1). The pyrazole compound exerted higher inhibitory effect both on the growth of planktonic cells and biofilm formation by penicillinase-positive and penicillinase-negative isolates of H. parainfluenzae than the activity of commonly used antibiotics such as ampicillin. No cytotoxicity of the tested compound in vitro at concentrations used was found. The tested pyrazole N-ethyl derivative could be considered as a compound for the design of agents active against both pathogenic H. influenzae and opportunistic H. parainfluenzae, showing also anti-biofilm activity. This appears important because biofilms are determinants of bacterial persistence in long-term and recurrent infections recalcitrant to standard therapy.

14.
Eur J Med Chem ; 60: 128-34, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23287058

RESUMO

A series of novel 1,2,4-triazole-ciprofloxacin hybrids was designed, synthesised and evaluated in vitro against drug-susceptible and drug-resistant bacteria. A significant part of the compounds obtained showed antibacterial activity higher than the activity of ciprofloxacin, both towards Gram-positive and Gram-negative species. Despite relatively small number of synthesised derivatives, it was possible to observe important dependences between their structure and activity.


Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Ciprofloxacina/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Triazóis/farmacologia , Antibacterianos/química , Células Cultivadas , Ciprofloxacina/química , Relação Dose-Resposta a Droga , Células HEK293 , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Triazóis/química
15.
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
16.
Arch Med Sci ; 8(1): 43-6, 2012 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-22457673

RESUMO

INTRODUCTION: The aim of the study was to examine the cytotoxicity and evaluate the antiviral and virucidal activity of methanol and methanol/H(2)O extracts from the herb of Peucedanum salinum. Plants belonging to the genus Peucedanum (Apiaceae family) have been used in traditional medicine for a long time. MATERIAL AND METHODS: The examination of the cytotoxicity of the extracts in the concentrations of 0.1, 0.2, 0.5, 1, 2, 4 mg/ml was carried out on the cell culture line HEK-293. Cytotoxicity of the examined extracts was measured by the colorimetric MTT (tetrazolium) method. After determination of the highest non-toxic concentration of examined extracts, antiviral and virucidal activity against adenovirus type 5 (Adenoviridae) was established. RESULTS: The non-toxic doses were as follows: 1 mg/ml of methanol extract and 2 mg/ml of methanol/H(2)O extract (1 : 1 v/v). Antiviral activity was observed for the methanol extract of Peucedanum salinum in concentrations of 0.5 and 1 mg/ml. The extract caused the decrease of titre of the virus by 2 log and 1.33 log, respectively. The methanol/H(2)O extract (1 : 1 v/v) decreased the titre of the virus by 1.33 log and 1.5 log in concentrations of 1 and 2 mg/ml, respectively. The examined extracts had no virucidal activity against adenovirus type 5. CONCLUSIONS: The examined extract is a new, potentially active source of active substances possessing antiviral activity and further studies are needed.

17.
Arch Pharm (Weinheim) ; 345(4): 302-13, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22009854

RESUMO

In an attempt to find a new class of antimicrobial agents, a series of benzothiazoles, 1,3-thiazolo[5,4-b]pyridines, 4H-3,1-benzothiazines, naphtho[2,3-d][1,3]thiazole-4,9-diones and other related compounds containing a 2,4-dihydroxyphenyl moiety were prepared. They were obtained via the reaction of aryl-modified sulfinyl[bis(2,4-dihydroxyphenylmethanethione)]s with appropriate commercial chemical reagents in the endocyclization processes. The MIC values of the compounds towards eight reference bacterial strains were assessed by the two-fold serial micro-dilution broth method. They exhibited inhibitory effects against the Gram-positive strains tested opposite to Gram-negative ones. Some compounds were more effective than the reference drug. 4-(6-Chloro-4H-3,1-benzothiazin-2-yl)-6-methylbenzene-1,3-diol (5b) due to its very good activity (MIC from 1.56 to 3.13 µg/mL) and low cytotoxicity (IC(50) > 50 µg/mL) may be regarded as a promising precursor for the development of novel antibacterial agents.


Assuntos
Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Tiazinas/síntese química , Tiazinas/farmacologia , Tiazóis/síntese química , Tiazóis/farmacologia , Anti-Infecciosos/química , Testes de Sensibilidade Microbiana/métodos , Testes de Sensibilidade Microbiana/estatística & dados numéricos , Estrutura Molecular , Relação Estrutura-Atividade , Tiazinas/química , Tiazóis/química
18.
Z Naturforsch C J Biosci ; 66(7-8): 333-9, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21950156

RESUMO

2-[(4-Methyl-4H-1,2,4-triazol-3-yl)sulfanyl]acetamide derivatives were synthesized and their structures were confirmed by 1H NMR, IR, and elemental analysis. Cytotoxicity of the compounds towards HEK-293 and GMK cells was evaluated. Moreover, the antiviral and virucidal activities of these compounds against human adenovirus type 5 and ECHO-9 virus were assessed. Some of the newly synthesized derivatives have the potential to reduce the viral replication of both tested viruses.


Assuntos
Acetamidas/síntese química , Acetamidas/farmacologia , Antivirais/síntese química , Antivirais/farmacologia , Triazóis/síntese química , Triazóis/farmacologia , Adenoviridae/efeitos dos fármacos , Linhagem Celular , Echovirus 9/efeitos dos fármacos , Humanos , Técnicas In Vitro , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Espectrofotometria Infravermelho
19.
Ann Agric Environ Med ; 15(2): 199-203, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19061255

RESUMO

Enteroviruses belong to the Picornaviridae family and are the smallest, nonenveloped viruses known to infect both humans and animals. The spread of enteroviral infections is mainly by the faecal-oral and oral-oral route, but also through direct contact with secretions from ophthalmic and dermal lesions. Water, food and soil contaminated by infected faeces are an exogenous infection source which creates many opportunities for the transfer of the infection, and cause an epidemic outbreak in a short period of time. Enteroviruses are being isolated from all types of water: ground, sea, sewage and fresh water environments but also--and what is the most important from the epidemiological point of view--drinking water. They are resilient organisms, able to withstand high concentrations of sodium chloride (NaCl) and large changes in temperature. These abilities allow the viruses to flourish in a water environment, their natural reservoir. The number of infections in temperate climate regions peak in summer months and early autumn. Detection of enteroviruses in the water environment is performed by virus isolation in cell cultures and the use of molecular techniques. Many researches conducted in different countries with the use of methods mentioned above, reveal widespread environmental contamination by enteroviruses.


Assuntos
Infecções por Enterovirus/epidemiologia , Enterovirus/efeitos dos fármacos , Enterovirus/crescimento & desenvolvimento , Saúde Pública , Microbiologia da Água , Surtos de Doenças/prevenção & controle , Reservatórios de Doenças/virologia , Enterovirus/isolamento & purificação , Infecções por Enterovirus/prevenção & controle , Infecções por Enterovirus/transmissão , Humanos , Polônia/epidemiologia , Prevalência , Estações do Ano , Cloreto de Sódio/farmacologia , Temperatura
20.
Bioorg Med Chem ; 15(16): 5480-6, 2007 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-17572093

RESUMO

The in vitro biological activities of novel derivatives of methyl and ethyl 2-(4-oxo-8-aryl-2H-3,4,6,7-tetrahydroimidazo[2,1-c][1,2,4]triazin-3-yl)acetates (3a, 3d-j) have been evaluated and are reported. The final heterobicycles (3a-j) were obtained from monocyclic 1-aryl-2-hydrazonoimidazolidines (2a-f) by addition and cyclization reaction with fumaric acid esters. In particular, compounds 3d and 3e were found to exhibit comparable antibacterial potencies in vitro as that of ampicillin. Heterobicycles of the 3e, 3g and 3j type were screened for their antiviral activities against the selected viruses' DNA (human adenovirus type 5-Ad-5) and RNA (human enterovirus-Echo-9). Simultaneously, their cytotoxicities towards HEK-293 and GMK cells were established. In particular, heterobicycle 3j, completely non-toxic for GMK cells, was found to exhibit virucidal properties against Echo-9 virus justifying its further investigation as the potential antiviral agent.


Assuntos
Antibacterianos/síntese química , Antibacterianos/toxicidade , Antivirais/síntese química , Antivirais/toxicidade , Ésteres/síntese química , Ésteres/toxicidade , Triazinas/química , Antibacterianos/química , Antivirais/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ésteres/química , Compostos Heterocíclicos/síntese química , Compostos Heterocíclicos/química , Compostos Heterocíclicos/toxicidade , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
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