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1.
J Agric Food Chem ; 68(6): 1514-1524, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-31977218

RESUMO

Pesticides coated to the seed surface potentially pose an ecological risk to granivorous birds that consume incompletely buried or spilled seeds. To assess the toxicokinetics of seeds treated with current-use fungicides, Japanese quail (Coturnix japonica) were orally dosed with commercially coated wheat seeds. Quail were exposed to metalaxyl, tebuconazole, and fludioxonil at either a low dose (0.0655, 0.0308, and 0.0328 mg/kg of body weight, respectively) or a high dose (0.196, 0.0925, and 0.0985 mg/kg of body weight, respectively). Fungicides were rapidly absorbed and distributed to tissues. Tebuconazole was metabolized into tert-butylhydroxy-tebuconazole. All compounds were eliminated to below detection limits within 24 h. The high detection frequencies observed in fecal samples potentially offer a non-invasive matrix to monitor pesticide exposure. With the summation of total body burden across plasma, tissue, and fecal samples, less than 9% of the administered dose was identified as the parent fungicide, demonstrating the importance to monitor both active ingredients and their metabolites in biological samples.


Assuntos
Coturnix/metabolismo , Fungicidas Industriais/metabolismo , Triazóis/metabolismo , Triticum/metabolismo , Animais , Transporte Biológico , Fezes/química , Fungicidas Industriais/análise , Fungicidas Industriais/toxicidade , Sementes/química , Sementes/metabolismo , Toxicocinética , Triazóis/análise , Triazóis/toxicidade , Triticum/química
2.
Chemosphere ; 241: 125129, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31683439

RESUMO

Tebuconazole is widely used as fungicide and has frequently been detected at elevated concentrations in environmental media. To characterize the potential toxicity of tebuconazole on vertebrate and humans. Using zebrafish as a vertebrate model, the toxic effects in liver that produced by low-toxic concentrations of tebuconazole were assessed in adult zebrafish. We further focused on tebuconazole-induced toxicity and its possible mechanism in larval zebrafish using a hepatotoxicity assay. The induction of oxidative stress in adult fish was evaluated by superoxide dismutase (T-SOD), catalase (CAT), peroxidase (POD), glutathione S-transferase (GST) activity, and the increased aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio. Significantly increased enzyme activity was observed in the liver of male and female fish at both exposure and depuration stage. Exposure to maximum non-lethal (MNLC) concentration of tebuconazole from 72 to 120 h post-fertilization (hpf) affected the liver size and yolk retention in larval zebrafish. Decreased fluorescence intensity was observed in larval Tg(Apo14:GFP) zebrafish, indicating liver degeneration after tebuconazole treated. Histopathological examination confirmed the alterations in liver histoarchitecture in exposed zebrafish. Significant 1.28-fold and 1.65-fold increases in reactive oxygen species levels were observed in juveniles exposed to MNLC and lethal concentration 10 (LC10) group, respectively. The acridine orange staining assay showed that apoptotic cells occurred in the liver regions. These results indicated that tebuconazole exposure resulted in impacts on the ecological risk in fish and vertebrate. Overall, the present study suggested further research in needed to better understand the tebuconazole-induced toxicity mechanism that associated with oxidative stress.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Estresse Oxidativo/efeitos dos fármacos , Triazóis/farmacologia , Peixe-Zebra/metabolismo , Animais , Apoptose/efeitos dos fármacos , Catalase/metabolismo , Feminino , Fungicidas Industriais/toxicidade , Larva/efeitos dos fármacos , Masculino , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Triazóis/toxicidade
3.
Environ Pollut ; 256: 113385, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31662261

RESUMO

Triazole resistance in Aspergillus fumigatus is a major cause of clinical inefficacy in the treatment of invasive aspergillosis (IA). The hypothesis that triazole fungicides have driven the development of resistance in A. fumigatus has garnered substantial attention due to the similar structure and global detection of antifungal resistant A. fumigatus (ARAF) isolates in the soil. However, there is little evidence linking the application of triazole fungicides to the emergence of ARAF in the soil. This study was conducted to test if the resistance in A. fumigatus and its associated mutations in cyp51A could be induced by propiconazole in liquid medium and soil. The results indicate that propiconazole can induce resistance by alteration of G138S in cyp51A, and the overexpression of cyp51A, AfuMDR3 and AfuMDR4. G138S in cyp51A was first detected in the soil and associated with resistance. The emergence of the ARAFs in the soil may depends upon the level of propiconazole, and the number of ARAFs in soil treated with propiconazole at 2- and 5-fold dose was much greater than those in soil treated at the recommended dosage. The current data indicate that propiconazole can induce triazole resistance in A. fumigatus and should be applied for agricultural purposes at levels at or below the recommended dosage to avoid the emergence of ARAF in the soil.


Assuntos
Antifúngicos/toxicidade , Aspergillus fumigatus/efeitos dos fármacos , Sistema Enzimático do Citocromo P-450/genética , Farmacorresistência Fúngica/efeitos dos fármacos , Proteínas Fúngicas/genética , Triazóis/toxicidade , Aspergillus fumigatus/genética , Farmacorresistência Fúngica/genética , Humanos , Testes de Sensibilidade Microbiana , Mutação , Solo/química , Microbiologia do Solo , Soluções
4.
Chemosphere ; 242: 125163, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31677518

RESUMO

The use of fungicides bears the risk of many undesirable outcomes that are manifested in, among other things, changes in the structure and activity of microorganisms. This study aimed at determining the effect of a Helicur 250 EW preparation, used to protect crops against fungal diseases, on the microbiological and biochemical activity of soil and on the development of Horderum vulgare L. The fungicide was sprayed on leaves of spring barley in the following doses (per active substance, i.e. tebuconazole, TEB): 0.046, 0.093, 0.139, 1.395, and 2.790 mg TEB plant-1. The following indices were analyzed in the study: index of microorganisms resistance (RS) to the effects of fungicide, microorganisms colony development index (CD), microorganisms ecophysiological diversity index (EP), genetic diversity of bacteria, enzymatic activity, and effect of the fungicide on spring barley development (IFH). The most susceptible to the effects of the fungicide turned out to be fungi. The metagenomic analysis demonstrated that the bacterial community differed in terms of structure and percentage contribution in the soil exposed to the fungicide from the control soil even at the Phylum level. However, Proteobacteria appeared to be the prevailing taxon in both soils. Bacillus arabhattai, B. soli, and B. simplex occurred exclusively in the control soil, whereas Ramlibacter tataounensis, Azospirillum palatum, and Kaistobacter terrae - exclusively in the soil contaminated with the fungicide. Helicur 250 EW suppressed activities of all soil enzymes except for arylsulfatase. In addition, it proved to be a strong inhibitor of spring barley growth and development.


Assuntos
Fungicidas Industriais/toxicidade , Hordeum/crescimento & desenvolvimento , Microbiota/efeitos dos fármacos , Microbiologia do Solo/normas , Poluentes do Solo/toxicidade , Triazóis/toxicidade , Bactérias/efeitos dos fármacos , Bactérias/enzimologia , Fungos/efeitos dos fármacos , Fungos/enzimologia , Fungicidas Industriais/análise , Metagenoma/efeitos dos fármacos , Microbiota/genética , Folhas de Planta/crescimento & desenvolvimento , Solo/química , Poluentes do Solo/análise , Triazóis/análise
5.
Chemosphere ; 242: 125209, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31677519

RESUMO

The fungicide myclobutanil (MYC) is a common contaminant found in surface water. The aim of this study was to determine the acute toxicity, developmental effects, bioconcentration factor (BCF) and potential bio-molecular mechanisms of MYC toxicity in zebrafish. Susceptibility to MYC toxicity was life-stage dependent with adult fish being the most sensitive (96 h-LC50, 6.34 mg/L) followed by 72 h post-hatch (hph) larvae (8.90 mg/L), 12 hph larvae (20.53 mg/L) and embryos (42.54 mg/L). Zebrafish embryos and larvae (12 hph) responded with decreased hatching, heartbeat and growth, as well as abnormal spontaneous movement and development. BCFs were calculated by quantifying MYC concentrations from different tissues of adult zebrafish exposed to MYC for up to 11 days. Highest BCFs were obtained from gills (18.25 ±â€¯0.07), followed by viscera (16.78 ±â€¯0.04), head (13.13 ±â€¯0.08) and muscle (8.96 ±â€¯0.10). MYC (0.5 mg/L) inhibited gene expression related to cholesterol synthesis pathway, including 24-dehydrocholesterol reductase (DHCR24), 7-dehydrocholesterol reductase (DHCR7), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCRa), HMGCRb, farnesyl-diphosphate farnesyltransferase 1(FDFT1), squa-lene epoxidase (SQLE), isopentenyl-diphosphate delta isomerase 1 (IDI1) and CYP51, while no cholesterol changes were observed in the MYC treated group. These results will contribute to the literature assessing the environmental risk of MYC in aquatic environment.


Assuntos
Colesterol/biossíntese , Nitrilos/toxicidade , Triazóis/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/crescimento & desenvolvimento , Animais , Bioacumulação , Colesterol/genética , Embrião não Mamífero/efeitos dos fármacos , Feminino , Fungicidas Industriais/toxicidade , Larva/efeitos dos fármacos , Estágios do Ciclo de Vida/efeitos dos fármacos , Masculino , Fatores Sexuais , Peixe-Zebra/metabolismo
6.
Ecotoxicol Environ Saf ; 190: 110085, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31855789

RESUMO

This study investigated the effects of paclobutrazol and profenofos on six neurotransmitters and their metabolites involving in cholinergic and non-cholinergic neurotransmission systems in mouse. The results revealed that profenofos decreased the levels of 5-hydroxyindole-3-acetic acid (5-HIAA) and normetanephrine (MNE), and increased the level of dopamine (DA) in the mice after four weeks of exposure. The turnovers of serotonergic neurotransmission system (5-HIAA/5-HT) and noradrenergic neurotransmission system (MNE/NE) showed a decline under exposure of profenofos. Exposure to paclobutrazol resulted in decreases of 5-HIAA and MNE in both sexes of mice, and of 5-HT and ACh in the females. Similar to profenofos, the turnovers of serotonergic neurotransmission system and noradrenergic neurotransmission system decreased in the mice exposed to paclobutrazol. The integrated biomarker response (IBR) was introduced to comprehensively evaluate the neurotoxic effects of the two pesticides through integration of the responses of neurotransmitters. The results of IBR indicated that the overall effect of neurotransmitters increased at the beginning of exposure and then decreased in the end. It was also found that the order of neurotoxic effect for the two pesticides is as: paclobutrazol > profenofos referred to their LD50. Furthermore, the effects on neurotransmitters are higher in the males.


Assuntos
Neurotransmissores/metabolismo , Organotiofosfatos/toxicidade , Praguicidas/toxicidade , Triazóis/toxicidade , Animais , Dopamina/metabolismo , Masculino , Camundongos
7.
Chemosphere ; 240: 124958, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31726587

RESUMO

Degradation of insensitive munitions (IMs) by ultraviolet (UV) light has become a topic of concern following observations that some UV-degradation products have increased toxicity relative to parent compounds in aquatic organisms. The present investigation focused on the Army's IM formulation, IMX-101, which is composed of three IM constituents: 2,4-dinitroanisole (DNAN), 3-nitro-1,2,4-triazol-5-one (NTO), and nitroguanidine (NQ). The IM constituents and IMX-101 were irradiated in a UV photo-reactor and then administered to Daphnia pulex in acute (48 h) exposures comparing toxicities relative to the parent materials. UV-degradation of DNAN had little effect on mortality whereas mortality for UV-degraded NTO and NQ (and associated degradation products) increased by factors of 40.3 and 1240, respectively, making UV-degraded NQ the principle driver of toxicity when IMX-101 is UV-degraded. Toxicity investigations for specific products formed during UV-degradation of NQ, confirmed greater toxicity than the parent NQ for degradation products including guanidine, nitrite, ammonia, nitrosoguanidine, and cyanide. Summation of the individual toxic units for the complete set of individually measured UV-degradation products identified for NQ only accounted for 25% of the overall toxicity measured in the exposures to the UV-degraded NQ product mixture. From these toxic unit calculations, nitrite followed by CN- were the principal degradation products contributing to toxicity. Given the underestimation of toxicity using the sum toxic units for the individually measured UV-degradation products of NQ, we conclude that: (1) other unidentified NQ degradation products contributed principally to toxicity and/or (2) synergistic toxicological interactions occurred among the NQ degradation product mixture that exacerbated toxicity.


Assuntos
Anisóis/química , Guanidinas/efeitos da radiação , Triazóis/química , Raios Ultravioleta , Animais , Anisóis/toxicidade , Daphnia/efeitos dos fármacos , Poluentes Ambientais/química , Poluentes Ambientais/toxicidade , Guanidinas/toxicidade , Mutação , Nitrocompostos/química , Nitrocompostos/toxicidade , Testes de Toxicidade , Triazóis/toxicidade
8.
Eur J Med Chem ; 185: 111824, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31708184

RESUMO

In searching for more effective and safer antiepileptic drugs, a series of 2,5-disubstituted [1,2,4]-triazolo[1,5-a]pyrimidine-7(4H)-one derivatives were designed and synthesized. Spontaneous Ca2+ oscillations (SCOs) of cortical neurons were used for in vitro phenotypic screening. Maximal electroshock test (MES) and pentylenetetrazole (PTZ) test were used to access their anticonvulsant activity, and rotarod test was used to estimate their neurotoxicity. The active compounds in in vitro model are specifically effective in pentylenetetrazole (PTZ)-induced epilepsy model but not maximal electroshock (MES) model, more importantly with lower neurotoxicity as compared to commonly used drugs. Among them, compound 5c and 5e showed significant anticonvulsant activities in PTZ-induced epilepsy model with ED50 values at 31.81 mg/kg and 40.95 mg/kg, respectively. These compounds have improved neurotoxicity with protective index (PI = TD50/ED50) values at 17.22 and 9.09, respectively. Finally we demonstrated that compound 5c and 5e mainly acted on GABAA receptor as positive modulators but not sodium channels. Thus the present study has provided potential candidates for further investigation in epilepsy.


Assuntos
Anticonvulsivantes/farmacologia , Atividade Motora/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Pirimidinas/farmacologia , Receptores de GABA-A/metabolismo , Convulsões/tratamento farmacológico , Triazóis/farmacologia , Animais , Anticonvulsivantes/química , Anticonvulsivantes/toxicidade , Células Cultivadas , Relação Dose-Resposta a Droga , Descoberta de Drogas , Eletrochoque , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Pentilenotetrazol , Substâncias Protetoras/química , Substâncias Protetoras/toxicidade , Pirimidinas/química , Pirimidinas/toxicidade , Convulsões/induzido quimicamente , Relação Estrutura-Atividade , Triazóis/química , Triazóis/toxicidade
9.
Environ Sci Pollut Res Int ; 26(34): 35253-35265, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31701422

RESUMO

Difenoconazole is a fungicide extensively used in agriculture. The aim of this study was to evaluate the effects of difenoconazole fungicide on the sperm quality of rats. Wistar rats were divided into four groups: control and exposed to 5 (D5), 10 (D10), or 50 mg-1 kg bw-1day (D50) of difenoconazole for 30 days, by gavage. Classical sperm parameters and surface-enhanced Raman scattering (SERS) were performed. Progressive motility, acrosomal integrity, and percentage of morphologically normal spermatozoa were reduced in the D10 and D50 groups in comparison with the control group. Sperm viability was reduced only in the D50 group. Sperm number in the testis and caput/corpus epididymis and daily sperm production were reduced in the three exposed groups. SERS measurements showed changes in the spectra of spermatozoa from D50 group, suggesting DNA damage. In addition, machine learning (ML) methods were used to evaluate the performance of three classification algorithms (artificial neural network-ANN, K-nearest neighbors-K-NN, and support vector machine-SVM) in the identification task of the groups exposed to difenoconazole. The results obtained by ML algorithms were very promising with accuracy ≥ 90% and validated the hypothesis of the exposure to difenoconazole reduces sperm quality. In conclusion, exposure of rats to different doses of the fungicide difenoconazole may impair sperm quality, with a recognizable classification pattern of exposure groups.


Assuntos
Dioxolanos/toxicidade , Fungicidas Industriais/toxicidade , Aprendizado de Máquina , Espermatozoides/efeitos dos fármacos , Triazóis/toxicidade , Animais , Dano ao DNA , Epididimo/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Análise Espectral Raman , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Máquina de Vetores de Suporte , Testículo/efeitos dos fármacos , Testes de Toxicidade
10.
Environ Pollut ; 255(Pt 2): 113309, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31610510

RESUMO

Azoles are effective antifungal agents used in both medicine and agriculture. They typically work by inhibiting cytochrome P450 enzymes, primarily CYP51 of the ergosterol biosynthesis pathway, thus damaging the fungal cell membrane. However, apart from their desired antifungal properties, several azoles also exhibit endocrine disrupting properties in mammals, both in vitro and in vivo. Here, we have tested two currently used agricultural azole fungicides, triticonazole and flusilazole, for their in vitro anti-androgenic activity and potential effects on reproductive parameters. Both fungicides showed strong androgen receptor (AR) antagonism and disruption of steroid biosynthesis in vitro. Following gestational exposure to flusilazole (15 or 45 mg/kg bw/day) or triticonazole (150 or 450 mg/kg bw/day) in time-mated Sprague Dawley rats, triticonazole induced shorter male anogenital distance (AGD). Flusilazole exposure did not affect the AGD, but altered fetal male blood hormone profile, with increased androstenedione and decreased estrone levels. Flusilazole and triticonazole have dissimilar effects on reproductive parameters in vivo, but both show endocrine disrupting activities.


Assuntos
Ciclopentanos/toxicidade , Disruptores Endócrinos/toxicidade , Fungicidas Industriais/toxicidade , Silanos/toxicidade , Triazóis/toxicidade , Antagonistas de Androgênios , Androstenodiona , Animais , Antifúngicos , Azóis , Masculino , Ratos , Ratos Sprague-Dawley , Reprodução/efeitos dos fármacos
11.
Environ Pollut ; 255(Pt 2): 113297, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31610514

RESUMO

Prothioconazole (PTC) is a widely used triazole fungicide with low toxicity, and its desulfurization metabolite, prothioconazole-desthio (PTC-d), is reported to have higher reproductive toxicity to mammals. However, little is known about the reproductive toxicity, much less endocrine disrupting effect, of these two chemicals on reptiles. In this study, we investigated the effects of single dose of PTC/PTC-d (100 mg kg-1 body weight) exposure on the pathomorphism of testes and epididymides, serum sex steroid hormones (testosterone and 17ß-estradiol) and transcription of steroidogenic-related genes (STARD, cyp11A, cyp17, cyp19A, 17ß-HSD, 3ß-HSD, AR and ER-α) in gonads of male lizards (Eremias argus). Although structural disorder existed in PTC-d exposure group, severe gonadal disruption, especially suppression of spermatogenesis was only observed in testis after PTC treatment, which consequently led to the lack of spermatozoa in epididymal ducts. Consistent with this result, T/E2 value in PTC exposure was elevated to a significant higher level compared with control and continually increased over time, while T/E2 value in the PTC-d exposure group slightly increased only at 12 h. These results demonstrated a more serious disruption of PTC on male lizard gonads than PTC-d. In addition, the expression of cyp17 gene was inhibited at 6 h, however, was induced at 12 h, and exhibited negative correlations with STARD, cyp11A and 3ß-HSD after PTC exposure at each timepoint. In PTC-d group, the expression of STARD and 3ß-HSD were significantly down-regulated, in contrast, cyp11A and cyp17 were up-regulated, and each gene showed consistent changes over time. For 17ß-HSD, no significance was observed in both treated groups. This study was the first to compare the gonadal disruption of PTC and PTC-d in male lizards and elucidated that these two chemicals influenced the physiological function of male gonads through differential transcriptional modulation.


Assuntos
Disruptores Endócrinos/toxicidade , Fungicidas Industriais/toxicidade , Lagartos/crescimento & desenvolvimento , Testículo/efeitos dos fármacos , Triazóis/toxicidade , Administração Oral , Animais , Estradiol/sangue , Lagartos/sangue , Masculino , Reprodução/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Testículo/patologia , Testosterona/sangue
12.
Environ Pollut ; 255(Pt 2): 113269, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31574395

RESUMO

Triazole fungicides are widely used in agriculture production and have adverse impacts on aquatic organisms. As one of the triazole fungicides, prothioconazole has been reported to cause many toxicological effects, but its risks to aquatic organisms are unknown. In this study, we systematically explored the toxicity effects of prothioconazole exposure on zebrafish embryos (Danio rerio) involving in developmental toxicity, oxidative damage and metabolism disorders. The results showed that prothioconazole exposure to zebrafish embryos produced a series of toxic symptoms, including hatching inhibition, shortening of body length, pericardial cyst and yolk cyst. In addition, prothioconazole exposure caused significant lipid peroxidation and oxidative damage. Particularly, we also found that metabolites and genes involved in lipid metabolism also showed significant changes. This study may provide theoretical basis for systematically assessing the potential risks of zebrafish embryos with prothioconazole exposure.


Assuntos
Embrião não Mamífero/fisiologia , Fungicidas Industriais/toxicidade , Triazóis/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/fisiologia , Animais , Organismos Aquáticos , Embrião não Mamífero/efeitos dos fármacos , Metabolismo dos Lipídeos , Peroxidação de Lipídeos , Poluentes Químicos da Água/análise , Peixe-Zebra/embriologia , Peixe-Zebra/metabolismo
13.
Ecotoxicol Environ Saf ; 185: 109691, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31563746

RESUMO

The rational use and the environmental safety of chiral pesticides have attracted significant research interest. Here, enantioselective toxic effects and the selective toxic mechanism of triticonazole (TRZ) against the aquatic microalgae Chlorella pyrenoidosa were studied. The 96h-EC50 values of rac-, (R)-(-)-, and (S)-(+)-TRZ were 1.939, 0.853, and 22.002 mg/L, respectively. At a concentration of 1 mg/L, the contents of photosynthetic pigments of C. pyrenoidosa exposed to (R)-(-)-TRZ were lower than if exposed to S-(+)-form and racemate. Transmission electron microscopic images showed that the R-(-)-form compromised the integrity of cells and disrupted the chloroplast structure. R-(-)-TRZ stimulated vast reactive oxygen species (ROS) and significantly increased superoxide dismutase (SOD) and catalase (CAT) activities, as well as malondialdehyde (MDA) content. For lipid accumulation experiments, nicotinamide adenine dinucleotide (NADH) and triacylglycerol (TAG) accumulations in algal cells treated with R-(-)-TRZ were 171.50% and 280.76%, respectively, compared with the control group. This far exceeded levels of algal cells treated with S-(+)- and rac-TRZ. Based on these data, R-(-)-TRZ was concluded to selectively affect the photosynthetic system, antioxidant system, and lipid synthesis of algal cells, thus causing enantioselective toxic effects of TRZ against C. pyrenoidosa, which indicating that the use of racemate may cause unpredictable environmental harm. Therefore, to reduce the hidden dangers of chiral pesticides for the ecological environment, the environmental risk of TRZ should be evaluated at the stereoselective level.


Assuntos
Chlorella/efeitos dos fármacos , Ciclopentanos/toxicidade , Fungicidas Industriais/toxicidade , Microalgas/efeitos dos fármacos , Triazóis/toxicidade , Poluentes Químicos da Água/toxicidade , Antioxidantes/metabolismo , Chlorella/metabolismo , Chlorella/ultraestrutura , Cloroplastos/efeitos dos fármacos , Cloroplastos/metabolismo , Ciclopentanos/química , Fungicidas Industriais/química , Malondialdeído/farmacologia , Microalgas/metabolismo , Microalgas/ultraestrutura , Fotossíntese/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Estereoisomerismo , Superóxido Dismutase/metabolismo , Triazóis/química , Poluentes Químicos da Água/química
14.
Arch Pharm (Weinheim) ; 352(10): e1900135, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31441087

RESUMO

A series of gatifloxacin-1,2,3-triazole-isatin hybrids 8a-l were designed, synthesized, and screened for their in vitro antimycobacterial activity as well as cytotoxicity toward Chinese Hamster Ovary (CHO) cells. The synthesized hybrids showed considerable activity against MTB H37 Rv and two MDR-MTB strains with minimal inhibitory concentration (MIC) of 0.25-8 µg/ml, and the hybrid 8a (MICMTB H37Rv : 0.25 µg/ml and MICMDR-MTB : 0.5 and 1 µg/ml) was found to be most active against the tested strains, which was not inferior to the parent gatifloxacin (MIC: 0.5, 0.25, and 0.5 µg/ml) against all three tested strains, and was ≥128-fold more active than isoniazid (MIC: ≥64 µg/ml) and rifampicin (MIC: >128 µg/ml) against the two MDR-MTB strains. Moreover, hybrid 8a (CC50 : 8.0 µg/ml) also displayed acceptable cytotoxicity toward CHO cells, and the selectivity index was 32. The structure-activity relationship and structure-cytotoxicity relationship were also enriched.


Assuntos
Antituberculosos/síntese química , Desenho de Drogas , Gatifloxacina/química , Isatina/química , Mycobacterium tuberculosis/efeitos dos fármacos , Triazóis/síntese química , Animais , Antituberculosos/química , Antituberculosos/farmacologia , Antituberculosos/toxicidade , Células CHO , Sobrevivência Celular/efeitos dos fármacos , Cricetinae , Cricetulus , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Triazóis/química , Triazóis/farmacologia , Triazóis/toxicidade
15.
Arch Pharm (Weinheim) ; 352(10): e1900092, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31463959

RESUMO

Due to their high specificity and efficacy, triazoles have become versatile antifungals to treat fungal infections in human healthcare and to control phytopathogenic fungi in agriculture. However, azole resistance is an emerging problem affecting human health as well as food security. Here we describe the synthesis of 10 novel {2-(3-R-1H-1,2,4-triazol-5-yl)phenyl}amines. Their structure was ascertained by liquid chromatography-mass spectrometry, 1 H and 13 C NMR, and elemental analysis data. Applying an in vitro growth assay, these triazoles show moderate to significant antifungal activity against the opportunistic pathogen Aspergillus niger, 12 fungi (Fusarium oxysporum, Fusarium fujikuroi, Colletotrichum higginsianum, Gaeumannomyces graminis, Colletotrichum coccodes, Claviceps purpurea, Alternaria alternata, Mucor indicus, Fusarium graminearum, Verticillium lecanii, Botrytis cinerea, Penicillium digitatum) and three oomycetes (Phytophtora infestans GL-1, P. infestans 4/91; R+ and 4/91; R-) in the concentration range from 1 to 50 µg/ml (0.003-2.1 µM). Frontier molecular orbital energies were determined to predict their genotoxic potential. Molecular docking calculations taking into account six common fungal enzymes point to 14α-demethylase (CYP51) and N-myristoyltransferase as the most probable fungal targets. With respect to effectiveness, structure-activity calculations revealed the strong enhancing impact of adamantyl residues. The shown nonmutagenicity in the Salmonella reverse-mutagenicity assay and no violations of drug-likeness parameters suggest the good bioavailability and attractive ecotoxicological profile of the studied triazoles.


Assuntos
Antifúngicos/síntese química , Desenho de Drogas , Fungos Mitospóricos/efeitos dos fármacos , Triazóis/síntese química , Antifúngicos/química , Antifúngicos/farmacologia , Antifúngicos/toxicidade , Testes de Sensibilidade Microbiana , Fungos Mitospóricos/crescimento & desenvolvimento , Simulação de Acoplamento Molecular , Estrutura Molecular , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Relação Estrutura-Atividade , Triazóis/química , Triazóis/farmacologia , Triazóis/toxicidade
16.
Biomarkers ; 24(7): 720-725, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31464141

RESUMO

Background: Fungicides describe all chemicals used to control fungi that infect plants. Luna Experience SC-400 is a new line of fungicide that consist of Fluopyram and Tebuconazole. Objective: In this study, We investigated the genotoxicty and cytotoxicty of Luna Experience-SC 400 using comet assay, micronucleus test and polychromatic erythrocytes number in rat bone marrow. The present study is the first report indicating the effects of genotoxic and cytotoxic of Luna experience SC-400 on rat bone marrow cells. Material and Methods: We used three different doses (5mg/kg, 10mg/kg, 20mg/kg) of Luna Experience SC 400 at 48 h intervals during 30 days by gavage in rats.Genotoxicity was evaluated using comet assay and micronucleus test and cytotoxicity was measured the PCE/NCE rate in rat bone marrow. Results: Based on these experimental results, we report that Luna Experience-SC 400 fungicide presents genotoxic and cytotoxic potential on rat bone marrow. There is a significant difference between negative control group and all the doses of Luna Experience-SC 400 (p < 0.05) for comet assay and micronucleus. Even moderate and high doses of fungicides seem to have reached the values of almost positive control group for Genetic Damage Index (GDI) and Damaged Cell Percentage (DCP). In this study, we also investigated the PCE/NCE rate. Fungicide caused a decrease in the level of significant in the PCE/NCE ratio (p < 0.05). Conclusion: Our in vivo study suggests that the gavage exposure to Luna experience SC 400 used in the present investigation may be genotoxic and cytotoxic in rat bone marrow in view of these findings. Because this findings is first report represented in the pesticide biology, it is important to carry out more investigations using various cytogenetic tests under different experimental conditions to definitively resolve the the possible genotoxic and cytotoxic risk associated with new generation pesticides-fungicides.


Assuntos
Benzamidas/toxicidade , Medula Óssea/efeitos dos fármacos , Fungicidas Industriais/toxicidade , Piridinas/toxicidade , Triazóis/toxicidade , Animais , Ensaio Cometa , Citotoxinas/farmacologia , Relação Dose-Resposta a Droga , Testes para Micronúcleos , Mutagênicos/farmacologia , Ratos
17.
J Environ Sci Health B ; 54(12): 964-971, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31429367

RESUMO

Sensitivity of 24 isolates of Colletotrichum destructivum O'Gara, collected from alfalfa plants in Serbia, to eight selected fungicides, was investigated in this study. Molecular identification and pathogenicity test of isolates tested were also performed. Fungicide sensitivity was evaluated in vitro, using mycelial growth assay method. All isolates exhibited significant pathogenicity, causing necrosis at the alfalfa seedling root tips two days after inoculation. Using the primer pair GSF1-SR1 and by comparing the amplified fragments of the tested isolates with the marker (M), the presence of the amplicon of the expected size of about 900 bp was determined for all isolates. The isolates tested in this study showed different sensitivity towards fungicides in vitro. Mycelial growth was highly inhibited by QoI (quinone outside inhibitors) fungicide pyraclostrobin (mean EC50=0.39 µg mL-1) and by DMI (demethylation-inhibiting) fungicide tebuconazole (mean EC50=0.61 µg mL-1), followed by azoxystrobin (mean EC50=2.83 µg mL-1) and flutriafol (mean EC50=2.11 µg mL-1). Multi-site fungicide chlorothalonil and MBC (methyl benzimidazole carbamate) fungicide thiophanate-methyl evinced moderate inhibition with mean EC50=35.31 and 62.83 µg mL-1, respectively. Thirteen isolates were sensitive to SDHI (succinate dehydrogenase inhibitors) fungicide boscalid and fluxapyroxad, (mean EC50=0.49 and 0.19 µg mL-1, respectively), while the rest of isolates were highly resistant.


Assuntos
Colletotrichum/efeitos dos fármacos , Fungicidas Industriais/toxicidade , Medicago sativa/microbiologia , Estrobilurinas/toxicidade , Colletotrichum/enzimologia , Colletotrichum/crescimento & desenvolvimento , Proteínas Fúngicas/antagonistas & inibidores , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Doenças das Plantas/microbiologia , Pirimidinas/toxicidade , Sérvia , Succinato Desidrogenase/antagonistas & inibidores , Succinato Desidrogenase/genética , Succinato Desidrogenase/metabolismo , Triazóis/toxicidade
18.
Ecotoxicol Environ Saf ; 182: 109375, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31299474

RESUMO

The continuous and extensive use of pesticides, particularly in the field of agriculture, leads to contamination of all ecosystems (water, soil, and atmosphere). Among pesticides, fungicides constitute a larger group whose impact on the environment are still poorly studied. Difenoconazole belongs to triazole group of fungicides having high photochemical stability and have low biodegradability, which makes them persistent in water bodies. The present study focuses on the physiological and cytotoxic impact of difenoconazole fungicide on ciliated protozoa, Tetrahymena pyriformis with reference to growth, morphology, behaviour and its generation time. Morphological studies showed changes in the shape and size of T. pyriformis. Our result showed an inhibitory effect on population growth of T. pyriformis and the IC50 concentration was found to be 6.8 µg mL-1.The numbers of generations decreased and generation time was found to be extended in a concentration and time dependent manner. Difenoconazole caused significant depletion in phagocytic activity and also ultra-structural changes were observed by Transmission electron microscopy (TEM) analysis. The results indicate that the Tetrahymena toxicity assay could be used as a complementary system to rapidly elucidate the cytotoxic potential of fungicide.


Assuntos
Dioxolanos/toxicidade , Fungicidas Industriais/toxicidade , Tetrahymena pyriformis , Triazóis/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Ecossistema , Tetrahymena pyriformis/efeitos dos fármacos , Tetrahymena pyriformis/fisiologia , Tetrahymena pyriformis/ultraestrutura
19.
Environ Sci Pollut Res Int ; 26(26): 27385-27395, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31325091

RESUMO

The environmental behavior of paclobutrazol in soil and its toxicity were studied by field investigation and an outdoor pot experiment, and the residue of paclobutrazol was detected by gas chromatography-mass spectrometry. Field investigation has found that the residual paclobutrazol in the former succession crop could severely inhibit the growth of succeeding crops of potato; with migration and transformation of residual paclobutrazol in the soil, the stems of potato were thickened with residual amount of 1.23 mg kg-1, the growth was slow, and the height of potato in soil with residual amount of 1.34 mg kg-1 and the control was significantly different. The degradation dynamics of paclobutrazol fits with the first-order degradation kinetics, although T1/2 of paclobutrazol of the taro planting soil was 30.14-46.21 days and the residual paclobutrazol remained detectable even on day 120 after application. Taro leaves were sensitive to the stress of paclobutrazol pollution; the taro leaf thickness increased, the leaf area decreased, the chlorophyll content per area unit of taro leaf showed an obvious increased trend, and SOD and CAT activities and MDA and proline content increased significantly. Paclobutrazol promoted the tillering of taro, and the taro seedlings were dwarfed by 58.01, 63.27, and 75.88% at different concentrations. It indicated that taro had strong stress response ability under paclobutrazol pollution.


Assuntos
Colocasia/efeitos dos fármacos , Poluentes do Solo/toxicidade , Solanum tuberosum/efeitos dos fármacos , Triazóis/toxicidade , Catalase/metabolismo , Clorofila/metabolismo , Colocasia/crescimento & desenvolvimento , Colocasia/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Proteínas de Plantas/metabolismo , Plântula/efeitos dos fármacos , Plântula/crescimento & desenvolvimento , Plântula/metabolismo , Solo/química , Poluentes do Solo/análise , Poluentes do Solo/química , Solanum tuberosum/crescimento & desenvolvimento , Solanum tuberosum/metabolismo , Superóxido Dismutase/metabolismo , Triazóis/análise , Triazóis/química
20.
Artigo em Inglês | MEDLINE | ID: mdl-31328643

RESUMO

The herbicide amicarbazone (AMZ), which appeared as a possible alternative to atrazine, presents moderate environmental persistence and is unlikely to be removed by conventional water treatment techniques. Advanced oxidation processes (AOPs) driven by •OH and/or SO4•- radicals are then promising alternatives to AMZ-contaminated waters remediation, even though, in some cases, they can originate more toxic degradation products than the parent-compound. Therefore, assessing treated solutions toxicity prior to disposal is of extreme importance. In this study, the toxicity of AMZ solutions, before and after treatment with different •OH-driven and SO4•--driven AOPs, was evaluated for five different microorganisms: Vibrio fischeri, Chlorella vulgaris, Tetrahymena thermophila, Escherichia coli, and Bacillus subtilis. In general, the toxic response of AMZ was greatly affected by the addition of reactants, especially when persulfate (PS) and/or Fe(III)-carboxylate complexes were added. The modifications of this response after treatment were correlated with AMZ intermediates, which were identified by mass spectrometry. Thus, low molecular weight by-products, resulting from fast degradation kinetics, were associated with increased toxicity to bacteria and trophic effects to microalgae. These observations were compared with toxicological predictions given by a Structure-Activity Relationships software, which revealed to be fairly compatible with our empirical findings.


Assuntos
Radical Hidroxila/química , Sulfatos/química , Triazóis/toxicidade , Poluentes Químicos da Água/toxicidade , Purificação da Água/métodos , Aliivibrio fischeri/efeitos dos fármacos , Chlorella vulgaris/efeitos dos fármacos , Compostos Férricos/química , Cinética , Oxirredução , Triazóis/análise , Poluentes Químicos da Água/análise
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