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1.
Toxicology ; 457: 152805, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33961950

RESUMO

Niclosamide (NIC), a helminthic drug used widely for controlling schistosomiasis, can reportedly disrupt the endocrine system. However, its underlying mechanisms are still unclear. In this study, we revealed the potential endocrine disruption mechanism of NIC by activating estrogen receptors (ERs) and estrogen-related receptors (ERRs). The binding potency of NIC with ERα, ERß and ERRγ were determined by fluorescence competitive binding assays, which shows an IC50 (the concentration of NIC needed to displace 50 % of the probe from the receptor) of 90 ± 4.1, 10 ± 1.7 nM and 0.59 ± 0.07 nM respectively. The IC50 for ERRγ is the lowest one among the three detected receptors, which is three orders of magnitude lower than the known agonist GSK4716.The transcriptional activities of NIC on ERs and ERRs were detected by MVLN cells (stably transfected with ERs reporter gene) and HeLa cells (transiently transfected with ERRs reporter gene)-based luciferase reporter gene assay. The lowest observable effective concentration (LOEC) ranked as follows: ERRγ (0.5 nM) < ERRα (10 nM) < ERs (100 nM). The maximum observed induction rate for ERRγ (294 %) was higher than that for ERRα (191 %). The maximum observed induction rate of NIC for ERs was 30 % relative to 17ß-estradiol. In addition, we simulated the interactions of NIC with ERs and ERRs by molecular docking. NIC could dock into the ligand binding pockets of ERs and ERRs and form hydrogen bonds with different amino acids. The binding energy ranked as follows: ERRγ (-8.90 kcal/mol) < ERß (-7.57 kcal/mol) < ERRα (-7.15 kcal/mol) < ERα (-6.53 kcal/mol), which implied that NIC bound to ERRγ with higher binding affinity than the other receptors. Overall, we clarify that ERRγ might be the dominant target for NIC in cells rather than ERRα and ERs. We reveal potential novel mechanisms for the endocrine disruption effects of NIC by activating both ERRs and ERs at environmentally-related nanomolar levels.


Assuntos
Disruptores Endócrinos/metabolismo , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Niclosamida/metabolismo , Receptores de Estrogênio/metabolismo , Anticestoides/metabolismo , Anticestoides/toxicidade , Relação Dose-Resposta a Droga , Disruptores Endócrinos/toxicidade , Células HeLa , Humanos , Células MCF-7 , Niclosamida/toxicidade , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/fisiologia , Estrutura Secundária de Proteína
2.
Chemosphere ; 244: 125468, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31790986

RESUMO

Niclosamide (NIC) is the most widely used molluscicides for preventing the occurrence of schistosomiasis disease, and its residues can be found in various environmental samples. However, the toxicity mechanism of NIC during early developmental stage remains largely unknown. In the present study, zebrafish embryos were acutely exposed to NIC at an environmentally realistic concentration (0 and 40 µg/L) until 120 h post-fertilization. Transcriptomic sequencing was performed to provide mechanistic insight into developmental impairment. Pathway enrichment analyses found that biological processes related to lipid metabolism were significantly affected in exposed zebrafish larvae. Consistently, biochemical measurements showed that NIC developmental exposure depleted lipid storage, elevated lipid utilization, but inhibited lipid synthesis. Furthermore, as characterized by pathway enrichment and hormonal levels, steroid hormone biosynthesis was also significantly disrupted by NIC exposure in zebrafish larvae, indicating the endocrine disrupting potential of NIC. Detoxifying phase I and II processes (e.g., metabolism, conjugation and elimination) were significantly activated by NIC exposure. Overall, our findings suggest that NIC developmental exposure at an environmentally realistic concentration disturbs the lipid metabolism, induces endocrine disruption and initiates detoxifying capacity in zebrafish larvae, which will provide preliminary clues for developmental toxicity mechanisms of NIC.


Assuntos
Anticestoides/toxicidade , Disruptores Endócrinos/toxicidade , Niclosamida/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Embrião não Mamífero/efeitos dos fármacos , Larva/metabolismo , Transcriptoma , Peixe-Zebra/metabolismo
3.
Toxicol Appl Pharmacol ; 334: 35-46, 2017 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-28867437

RESUMO

Quinacrine, which is clinically used as an antimalarial drug, has anti-cancer activity. However, mechanism underlying its cytotoxic effect remains to be completely elucidated. In the present study, we investigated the cytotoxic effect of quinacrine on human leukemia U937 cells. Quinacrine-induced apoptosis of U937 cells was accompanied with ROS generation, mitochondrial depolarization, and BAX upregulation. Quinacrine-treated U937 cells showed ROS-mediated p38 MAPK activation and ERK inactivation, which in turn upregulated FOXP3 transcription. FOXP3-mediated miR-183 expression decreased ß-TrCP mRNA stability and suppressed ß-TrCP-mediated SP1 degradation, thus increasing SP1 expression in U937 cells. Upregulated SP1 expression further increased BAX expression. BAX knock-down attenuated quinacrine-induced mitochondrial depolarization and increased the viability of quinacrine-treated cells. Together, our data indicate that quinacrine-induced apoptosis of U937 cells is mediated by mitochondrial alterations triggered by FOXP3/miR-183/ß-TrCP/SP1 axis-mediated BAX upregulation.


Assuntos
Fatores de Transcrição Forkhead/metabolismo , MicroRNAs/metabolismo , Quinacrina/toxicidade , Fator de Transcrição Sp1/metabolismo , Proteína X Associada a bcl-2/metabolismo , Proteínas Contendo Repetições de beta-Transducina/metabolismo , Anticestoides/toxicidade , Apoptose/efeitos dos fármacos , Fatores de Transcrição Forkhead/genética , Regulação da Expressão Gênica/fisiologia , Técnicas de Silenciamento de Genes , Humanos , Leucemia , MicroRNAs/genética , Fator de Transcrição Sp1/genética , Células U937 , Proteína X Associada a bcl-2/genética , Proteínas Contendo Repetições de beta-Transducina/genética
4.
PLoS One ; 7(4): e35033, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22536349

RESUMO

Parasitic flatworms are responsible for serious infectious diseases that affect humans as well as livestock animals in vast regions of the world. Yet, the drug armamentarium available for treatment of these infections is limited: praziquantel is the single drug currently available for 200 million people infected with Schistosoma spp. and there is justified concern about emergence of drug resistance. Thioredoxin glutathione reductase (TGR) is an essential core enzyme for redox homeostasis in flatworm parasites. In this work, we searched for flatworm TGR inhibitors testing compounds belonging to various families known to inhibit thioredoxin reductase or TGR and also additional electrophilic compounds. Several furoxans and one thiadiazole potently inhibited TGRs from both classes of parasitic flatworms: cestoda (tapeworms) and trematoda (flukes), while several benzofuroxans and a quinoxaline moderately inhibited TGRs. Remarkably, five active compounds from diverse families possessed a phenylsulfonyl group, strongly suggesting that this moiety is a new pharmacophore. The most active inhibitors were further characterized and displayed slow and nearly irreversible binding to TGR. These compounds efficiently killed Echinococcus granulosus larval worms and Fasciola hepatica newly excysted juveniles in vitro at a 20 µM concentration. Our results support the concept that the redox metabolism of flatworm parasites is precarious and particularly susceptible to destabilization, show that furoxans can be used to target both flukes and tapeworms, and identified phenylsulfonyl as a new drug-hit moiety for both classes of flatworm parasites.


Assuntos
Anticestoides/farmacologia , Antiplatelmínticos/farmacologia , Echinococcus granulosus/efeitos dos fármacos , Fasciola hepatica/efeitos dos fármacos , Proteínas de Helminto/antagonistas & inibidores , Complexos Multienzimáticos/antagonistas & inibidores , NADH NADPH Oxirredutases/antagonistas & inibidores , Animais , Anticestoides/química , Anticestoides/toxicidade , Antiplatelmínticos/química , Antiplatelmínticos/toxicidade , Linhagem Celular , Avaliação Pré-Clínica de Medicamentos , Echinococcus granulosus/enzimologia , Fasciola hepatica/enzimologia , Fibroblastos/efeitos dos fármacos , Proteínas de Helminto/química , Humanos , Larva/efeitos dos fármacos , Larva/enzimologia , Linfócitos/efeitos dos fármacos , Camundongos , Modelos Moleculares , Complexos Multienzimáticos/química , NADH NADPH Oxirredutases/química , Oxidiazóis/química , Oxidiazóis/farmacologia , Oxidiazóis/toxicidade , Teoria Quântica , Quinoxalinas/química , Quinoxalinas/farmacologia , Quinoxalinas/toxicidade , Relação Estrutura-Atividade , Tiadiazóis/química , Tiadiazóis/farmacologia , Tiadiazóis/toxicidade
5.
Trans R Soc Trop Med Hyg ; 104(4): 304-6, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19716575

RESUMO

As a new suspension concentrate of niclosamide (SCN) was more effective in controlling Oncomelania snails than a wettable powder of the same drug, it was tested against Biomphalaria glabrata. There were no differences in the effect of the suspension concentrate, the wettable powder of niclosamide and ball-milled pure niclosamide against the adult snails, but at after 48h 0.125mg/l SCN killed 100% of eggs compared with 84.3% for WPN and 17.7% for pure niclosamide. Because of the improved handling characteristics of SCN over the other formulations, further field tests on Biompharia and Bulinus species are warranted.


Assuntos
Anticestoides/toxicidade , Biomphalaria/efeitos dos fármacos , Niclosamida/toxicidade , Animais , Esquistossomose/prevenção & controle , Testes de Toxicidade
6.
World J Surg ; 31(6): 1280-3, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17446990

RESUMO

Octenidine HCl is new topical antiseptic solution for wounds and abdominal washing that has been found to be highly effective for inactivating scolices in an in vitro study. However, the effects of octenidine HCl on the liver are not yet known. The aim of this study was to determine if there are any histopathologic changes after injecting octenidine HCl into the liver. A group of 50 male Sprague-Dawley rats were included in the study and randomly divided into five groups of 10 rats each, as follows: sham group; 0.09% NaCl group; 20% NaCl group; undiluted octenidine HCl group; 1% octenidine HCl group. The scolicidal agents (0.3 ml) were directly injected into the left lobe of the liver (except in the sham group). At 3 and 7 days after the injection, the rats were sacrificed, and the left lobe of the liver was harvested. Liver tissue was scored for degree of necrosis and the diameter of the necrosis examined under light microscopy. The highest scores were found in the undiluted octenidine HCl group, although a similar effect was observed in the 20% NaCl group. There was no necrosis in the sham group, the 0.09% NaCl group, or the 1% octenidine HCl group. All of the injury was coagulation-type necrosis. No mortality was observed throughout the study. The 1% octenidine HCl solution could thus be used as a scolicidal agent in liver tissue, whereas the undiluted form of octenidine and 20% NaCl solutions were shown to cause necrosis when directly injected into liver tissue in our animal model.


Assuntos
Anti-Infecciosos Locais/toxicidade , Anticestoides/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/patologia , Piridinas/toxicidade , Animais , Anti-Infecciosos Locais/administração & dosagem , Anticestoides/administração & dosagem , Relação Dose-Resposta a Droga , Iminas , Injeções , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Piridinas/administração & dosagem , Ratos , Ratos Sprague-Dawley
7.
Parasitol Res ; 89(6): 467-72, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12658458

RESUMO

We recently standardised Mesocestoides vogae (syn. corti) tetrathyridia cultures in the presence of sodium taurocholate. Parasite clustering and segmentation were observed as taurocholate-dependent effects in biphasic and monophasic media, respectively, and both were inhibited by a specific minimum inhibitory concentration (m.i.c.) of the cestocidal drugs albendazol and praziquantel. In the present study, we analysed the relationship between clustering inhibition and drug toxicity using praziquantel and a mouse experimental infection. In an "in vitro-in vivo" trial, a significant (ANOVA, P<0.05) reduction was observed in the infectivity of tetrathyridia previously cultured with praziquantel m.i.c. (0.06 micro g/ml) for 10 days. In an "in vivo-in vitro" trial, the clustering of tetrathyridia recovered from mice treated with praziquantel was found to be markedly reduced: 22%, compared with 83% cluster-containing wells of parasites from control mice. These results show that the outcome of infection and the suppression of taurocholate-induced clustering provide consistent indications of praziquantel toxicity against M. vogae, an observation confirmed by histological studies. The easily recorded clustering inhibition of M. vogae tetrathyridia in biphasic medium is a potentially useful system for the assessment of drug toxicity against cestode larvae.


Assuntos
Anticestoides/toxicidade , Mesocestoides/efeitos dos fármacos , Testes de Sensibilidade Parasitária , Praziquantel/toxicidade , Animais , Anticestoides/farmacologia , Meios de Cultura , Histocitoquímica , Larva/efeitos dos fármacos , Larva/fisiologia , Masculino , Mesocestoides/crescimento & desenvolvimento , Camundongos , Praziquantel/farmacologia
9.
Eur Surg Res ; 30(6): 433-8, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9838237

RESUMO

The use of scolocidal solutions in the hepatobiliary system may result in caustic sclerosing cholangitis. In this study, the effectivenes of a biological metabolite of albendazole, albendazole sulfoxide, on scolices and the hepatobiliary system was evaluated. In the in vitro study, it was found that 100 microg/ml albendazole sulfoxide solution had strong scolocidal effect in 15 min. In the in vivo study, two experimental groups, each consisting of 8 rabbits aged 3-4 months and weighing 2,500 +/- 250 g, 100 microg/ml albendazole sulfoxide and normal saline were given into the biliary tract. ALP, GGT, SGOT and SGPT values on days 7, 30 and 60 were not found to be significantly increased compared to preoperative values. Total bilirubin values were high in the working group 7 and 30 days postoperatively and on day 30 in the control group, returning back to normal levels on day 60 in both groups. Histopathological evaluation of the liver parenchyma and the biliary system on day 60 revealed no differences between the groups. Consequently, albendazole sulfoxide solution may be used intraoperatively for scolocidal purposes.


Assuntos
Albendazol/análogos & derivados , Anticestoides/farmacologia , Sistema Biliar/efeitos dos fármacos , Equinococose Hepática/tratamento farmacológico , Fígado/efeitos dos fármacos , Alanina Transaminase/sangue , Albendazol/farmacologia , Albendazol/toxicidade , Fosfatase Alcalina/sangue , Animais , Anticestoides/toxicidade , Aspartato Aminotransferases/sangue , Sistema Biliar/patologia , Sistema Biliar/fisiopatologia , Bilirrubina/sangue , Colangite Esclerosante/induzido quimicamente , Equinococose Hepática/parasitologia , Echinococcus/efeitos dos fármacos , Humanos , Técnicas In Vitro , Fígado/patologia , Fígado/fisiopatologia , Coelhos , Ovinos , Fatores de Tempo , gama-Glutamiltransferase/sangue
10.
Med Parazitol (Mosk) ; (2): 38-40, 1998.
Artigo em Russo | MEDLINE | ID: mdl-9691620

RESUMO

In autobred albino mice, the maximum nonlethal dose of the agent CK-1 was established, which was 19.0 g/kg, the agent was nontoxic. Cotton rats aged 30-45 days were infected by alveococcosis from a donor rat. The methods and formulas developed by Mikhailitsin et al. were used during experiments and investigations. At the beginning of treatment, 5 rats were found to have a great deal of parasitic larvocysts (PL) 10 days after infection. Eight rats formed a control group, 8 were treated with CK-1 in a constantly increasing doses of 0.1, 0.26, and 0.34 g/kg for 3 weeks. Following 40 days of infection, the animals were anesthesized and CK-1 was ascertained to have a high antialveococcal activity: the index of suppressed PL growth was 90.23 to 92.74%. In 14 piglets aged 1 month, infected by echinococcosis strains and treated CK-1 in high doses, was established to cause echinococcal death. In 14 puppies, the agent was highly effective in strobular echinococcosis.


Assuntos
Anticestoides/uso terapêutico , Modelos Animais de Doenças , Equinococose/tratamento farmacológico , Animais , Anticestoides/toxicidade , Cães , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Equinococose/parasitologia , Feminino , Masculino , Camundongos , Sigmodontinae , Suínos , Fatores de Tempo
11.
Med Parazitol (Mosk) ; (4): 42-4, 1998.
Artigo em Russo | MEDLINE | ID: mdl-10050555

RESUMO

Experiments were made on 26-month-old piglets divided into 4 groups: Groups 1 and 4 included 5 piglets and Groups 2 and 3 comprised 8 animals. The piglets from Groups 1, 2, and 3 were peritoneally inoculated with 5000 protoscolices and acephalocysts of Echinococcus from patients with echinococcosis who had been operated on. On postinoculation day 60, Group 1 piglets were killed to measure the baseline weight of parasitic larvocysts (PL) developed by that time. On postinoculation day 61, Group 3 piglets continuously received feed in combination with CK-1 within 3 weeks. The mean daily doses of the agent were 0.05, 0.10, 0.25 g/kg, respectively. On day 91 following inoculation, all the animals were killed and dissected. The studies were made by using the procedures and formulas [9]. The growth suppression index for PL was 94.50, 92.39, and 96 for Groups 1, 2, and 3, respectively. Significant destruction of embryonic elements was revealed in 75-85% of PL in each treated animals. There was a tendency for blood indices to become normal in the treated animals. The acute toxicity of CK-1 was examined in outbred white mice, albino rats, chickens, piglets. The maximum non-lethal dose of CK-1 was 19 g/kg for white mice. The agent showed a low toxicity.


Assuntos
Anticestoides/uso terapêutico , Equinococose/tratamento farmacológico , Doenças dos Suínos/tratamento farmacológico , Animais , Anticestoides/toxicidade , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Equinococose/transmissão , Feminino , Humanos , Masculino , Camundongos , Extratos Vegetais/uso terapêutico , Extratos Vegetais/toxicidade , Ratos , Suínos , Doenças dos Suínos/transmissão , Fatores de Tempo
12.
Med Parazitol (Mosk) ; (4): 36-9, 1996.
Artigo em Russo | MEDLINE | ID: mdl-9026672

RESUMO

The paper outlines a procedure for manufacturing the anthelminthic Azinox (biltricide) using the new interfacial transfer catalyst benzyl-di-propyl (beta-hydroxyethyl)ammonium chloride. Azinox has been shown to be identical to biltricide (praziquantel) in its properties. Azinox tests on models of Opisthorchis felineus in golden hamsters and of Hymenolepis nana in albino outbred mice have indicated that the agent is not inferior to biltricide in its antitrematodal and anticestodal activities. Azinox displayed a high activity at the preimaginal stages of O. felineus and H. nana and at the larval stage of H.nana.


Assuntos
Anticestoides/síntese química , Antiplatelmínticos/síntese química , Praziquantel/análogos & derivados , Animais , Anticestoides/uso terapêutico , Anticestoides/toxicidade , Antiplatelmínticos/uso terapêutico , Antiplatelmínticos/toxicidade , Cricetinae , Avaliação Pré-Clínica de Medicamentos , Feminino , Himenolepíase/tratamento farmacológico , Himenolepíase/parasitologia , Dose Letal Mediana , Masculino , Mesocricetus , Camundongos , Opistorquíase/tratamento farmacológico , Opistorquíase/parasitologia , Praziquantel/síntese química , Praziquantel/uso terapêutico , Praziquantel/toxicidade
13.
Med Parazitol (Mosk) ; (3): 38-42, 1996.
Artigo em Russo | MEDLINE | ID: mdl-9036282

RESUMO

The paper describes the synthesis of the new agent G-1697 which is 4-[(benzo-2,1,3-thiadiazolyl-4)amino]-5, 6,7,8-tetrahydrobenzothieno [2,3-d] pyrimidine and the results of testing its acute toxicity and antiparasitic activity on a model of Echinococcus multilocularis invasion at the larval stage in cotton rats. The maximum nonlethal dose of G-1697 was 4.0 g/kg for outbred mice of both sexes whose weight was 14-16 g. Adult cotton rats (males) received the agent with their feed in increasing daily doses for 3 weeks continuously on days 8 to 28 after infection. The daily dose of its active ingredient varied from 0.03 to 0.35 g/kg and averaged 0.12 g/kg (the mean total dose per session was 2.47 g/kg). The baseline weight of parasitic larvocysts (PL) per animal averaged 0.28 g at the baseline. In the treated and control rats sacrificed 34 days following infection, the mean mass of PL per animal was 0.95 and 7.51 g, respectively. In the cotton rats treated with G-1697, the suppressed growth index calculated by three parameters (moderate, maximum, and minimum mass of PL in the animals of the comparable groups after treatment with regard to the similar baseline variables) was 90.8, 91.0 and 92.7, respectively, versus the controls. Among all PL found in each animal, its death was approximately 70-90% in the treated rats.


Assuntos
Anticestoides/síntese química , Pirimidinas/síntese química , Tiadiazóis/síntese química , Animais , Anticestoides/uso terapêutico , Anticestoides/toxicidade , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Equinococose/tratamento farmacológico , Equinococose/parasitologia , Echinococcus/efeitos dos fármacos , Feminino , Larva/efeitos dos fármacos , Masculino , Camundongos , Pirimidinas/uso terapêutico , Pirimidinas/toxicidade , Sigmodontinae , Tiadiazóis/uso terapêutico , Tiadiazóis/toxicidade , Fatores de Tempo
15.
Mutat Res ; 335(3): 235-43, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8524338

RESUMO

The potential metabolites of nitroscanate(4-isothiocyanato-4'-nitrodiphenyl ether) such as 4-amino-4'-nitrodiphenyl ether (ANDE), 4-acetamido-4'-nitrodiphenyl ether (AcNDE), 4-acetamido-4'-nitrosodiphenyl ether (4-N = 0), 4-acetamido-4'-hydroxylaminodiphenyl ether (4-NHOH), 4-acetamido-4'-acetohydroxamicdiphenyl ether [4-N(OH)Ac], 4-acetamido-4'-formohydroxamicdiphenyl ether [4-N(OH)CHO] and 4-acetamido-4'-acetylaceto-hydroxamicdiphenyl ether [4-N(OAc)Ac] were synthesized and investigated in the standard Salmonella mutagenicity test using TA98, TA98NR, TA98/1,8-DNP6, TA100 and TA100NR as indicator strains, in the presence and absence of hepatic S9. The relative order of activity among nitro and its reduction products, 4-N = 0 and 4-NHOH in TA98 and TA100 was 4-N = 0 > 4-NHOH > AcNDE. In nitroreductase deficient strain TA98NR, AcNDE was inactive, but expressed a slight activity in TA100NR while 4-N = 0 and 4-NHOH showed a large increase in specific activity in both the strains. In O-acetyltransferase deficient strain TA98/1,8-DNP6, AcNDE was inactive, while 4-N = O and 4-NHOH showed a sharp fall in activity. The hydroxylamine derived products with an activity order 4-N(OAc)Ac > 4-N(OH)CHO > 4-N(OH)Ac in both TA98 and TA100, showed 3-6 times increase in the specific activity for the latter two compounds in the presence of S9 mix, which was inhibited in the presence of paraoxan, indicating N-deacylation as an important metabolic activation pathway. Except the 4-NO in TA100, the observed mutagenicity of nitroscante (NSC) was higher than those of potential metabolites and the nor-isothiocyanato derivative 4'-nitrodiphenyl ether, thereby showing that -NCS function has a potentiating effect on the mutagenicity of this drug.


Assuntos
Anticestoides/toxicidade , Éteres Fenílicos/toxicidade , Salmonella typhimurium/efeitos dos fármacos , Tiocianatos/toxicidade , Animais , Biotransformação , Desenho de Fármacos , Fígado/metabolismo , Camundongos , Testes de Mutagenicidade , Mutagênicos/toxicidade , Éteres Fenílicos/metabolismo , Salmonella typhimurium/genética , Tiocianatos/metabolismo
16.
Mutat Res ; 334(3): 273-81, 1995 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7753091

RESUMO

Nitroscanate (NSC) was found to be a direct acting mutagen in the Ames Salmonella tester strains TA100 and TA98 and this activity increased further in the presence of rat liver S9 mix. It was inactive in TA98NR and TA100NR, and weakly active in TA98/1,8-DNP6. A substantial fall in drug induced mutagenicity by pentachlorophenol, an inhibitor of acetyltransferase, in TA98, TA100 and YG1024 suggests the initial bioconversion of a nitro group to hydroxylamine and its further activation to the ultimate N-acetoxyarylamine. The refrigerated DMSO solution of the drug in the plate incorporation assay and freshly prepared solutions using the pre-incubation procedure indicated a fall in mutagenicity owing to the conversion of NSC to N,N'-bis-4-(p-nitrophenoxy)phenyl thiourea (NFPT). The drastic reduction in mutagenicity in the presence of 4-amino-4'-nitrodiphenyl ether (ANDE) and 4-aminodiphenyl ether (ADE) was also attributed to the conversion of NSC to the corresponding thiourea, a non-mutagen. The negligible mutagenicity of ANDE and its absence in ADE and 4-isothiocyanate diphenyl ether (ITDE) suggests that the mutagenicity of NSC is due to the nitro group, and the -NCS function is responsible for enhanced mutagenicity over nor-isothiocyanate 4-nitrodiphenyl ether (NDE).


Assuntos
Anti-Helmínticos/toxicidade , Mutagênicos , Éteres Fenílicos/toxicidade , Tiocianatos/toxicidade , Acetiltransferases/efeitos dos fármacos , Anticestoides/toxicidade , Relação Dose-Resposta a Droga , Mutagênese , Testes de Mutagenicidade , Pentaclorofenol/farmacologia , Éteres Fenílicos/farmacologia , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Relação Estrutura-Atividade , Tioureia/análogos & derivados
18.
Med Parazitol (Mosk) ; (3): 41-4, 1994.
Artigo em Russo | MEDLINE | ID: mdl-7799857

RESUMO

The paper describes the synthesis of 6-[4-alkylpiperazinyl-1)phenylamino]-1,2,5-thiadiazolo[3,4-h ]quinolines where methyl (Drug G-1574) and ethyl (Drug G-1569) are alkyls. The two agents are as effective as mebendazole against the larval stage of Echinococcus multilocularis infection. Drug G-1574 has been demonstrated to ensure 100% recovery of spontaneously Hymenolepis nana-infected albino mice given doses 2.5-5 times lower than the effective dose of phenasal (niclosamide).


Assuntos
Anticestoides/síntese química , Anticestoides/uso terapêutico , Equinococose/tratamento farmacológico , Himenolepíase/tratamento farmacológico , Quinolinas/síntese química , Quinolinas/uso terapêutico , Animais , Anticestoides/toxicidade , Avaliação Pré-Clínica de Medicamentos , Equinococose/parasitologia , Feminino , Himenolepíase/parasitologia , Masculino , Mebendazol/uso terapêutico , Camundongos , Niclosamida/uso terapêutico , Quinolinas/toxicidade , Sigmodontinae
20.
Med Parazitol (Mosk) ; (5): 55-7, 1991.
Artigo em Russo | MEDLINE | ID: mdl-1758368

RESUMO

The synthesis and the acute toxicity and anticestodal activity of l-alkyl-4-[-(heterylamino)phenyl]-piperazines are presented. These compounds were found to be able to suppress the growth of larvocysts of Echinococcus multilocularis in cotton rats when injected intraperitoneally in a single dose of 0.25 g/kg, close to capacity of mebendazole. The tested compounds were also highly effective against the adult stage of Hymenolepis nana. Experimentally infected mice given an oral single dose of 0.2-0.5 g/kg of the drug were radically cured.


Assuntos
Anticestoides/síntese química , Equinococose/tratamento farmacológico , Himenolepíase/tratamento farmacológico , Piperazinas/síntese química , Animais , Anticestoides/uso terapêutico , Anticestoides/toxicidade , Avaliação Pré-Clínica de Medicamentos , Feminino , Masculino , Camundongos , Piperazinas/uso terapêutico , Piperazinas/toxicidade , Sigmodontinae
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