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1.
J Agric Food Chem ; 67(43): 12129-12136, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31593462

RESUMO

To explore lead compounds for biological insecticides, nine fatty acids (FAs)' insecticidal activities against Helicoverpa zea (Lepidoptera, Noctuidae) and their cytotoxicity on H. zea neuronal cells (AW1 cells) were evaluated. The results showed that FAs at 1000 mg/L had a mortality rate of 10.0-83.33% and an inhibitory rate on AW1 cells with IC50 values of 74.6-287.37 µM. Particularly, lauric acid exhibited the most excellent bioactivity both in vivo and in vitro among nine FAs. Further, its mode of action was investigated on the AW1 cells, and the results showed that lauric acid induced apoptosis on the AW1 cells, involving a decrease of mitochondrial membrane potential (ΔΨm) and an increase of caspase-9/3 activity and reactive oxygen species (ROS) levels. Furthermore, by detecting the expression of apoptosis protein, we found that the levels of Bcl-2 fell whereas the levels of cytochrome c and Bax rose remarkably. These results showed that FAs such as lauric acid could be potential lead compounds with a novel mode of action and highly insecticidal activity against H. zea.

2.
Pestic Biochem Physiol ; 158: 175-184, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31378354

RESUMO

Succinate dehydrogenase (SDH), an essential component of cellular respiratory chain and tricarboxylic acid (or Krebs) cycle, has been identified as one of the most significant targets for pharmaceutical and agrochemical. Herein, with the aim of discovery of new antifungal lead structures, a class of novel N-(4-fluoro-2-(phenylamino)phenyl)-pyrazole-4-carboxamides were designed, synthesized and evaluated for their biological activities. They were bioassayed against seven phytopathogenic fungi, Rhizoctonia solani, Phytophthora infestans, Fusarium oxysporum f. sp. vasinfectum, Botryosphaeria dothidea, Gibberella zeae, Alternaria alternate and Fusarium oxysporum f. sp. niveum. The results indicated that most of the compounds displayed good antifungal activities, especially against R. solani. Among them, compounds 7 and 12 exhibited higher antifungal activities against R. solani in vitro with EC50 value of 0.034 mg/L and 0.021 mg/L, being superior to the commercially available fungicide bixafen (EC50 = 0.043 mg/L). Pot tests against R. solani showed that in vivo EC50 values of compounds 7 (2.694 mg/L) and 12 (2.331 mg/L) were higher than that of bixafen (3.724 mg/L). In addition, inhibitory activity of compound 12 against SDH indicated compound 12 (IC50 = 1.836 mg/L) showed good inhibitory activity against SDH, being close to bixafen's inhibitory activity (IC50 = 1.222 mg/L). And, molecular modeling of the SDH-compound 12 complex suggested that compound 12 could strongly bind to and interact with the binding site of the SDH. The results of the present work showed that N-(4-fluoro-2-(phenylamino)phenyl)-pyrazole-4-carboxamides were a new fungicides for discovery of SDH inhibitors and worth further study.


Assuntos
Antifúngicos/química , Antifúngicos/farmacologia , Succinato Desidrogenase/metabolismo , Alternaria/efeitos dos fármacos , Alternaria/enzimologia , Ascomicetos/efeitos dos fármacos , Ascomicetos/enzimologia , Fusarium/efeitos dos fármacos , Fusarium/enzimologia , Phytophthora infestans/efeitos dos fármacos , Phytophthora infestans/enzimologia , Rhizoctonia/efeitos dos fármacos , Rhizoctonia/enzimologia , Relação Estrutura-Atividade
3.
Pestic Biochem Physiol ; 157: 169-177, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31153465

RESUMO

To explore the toxicity mechanisms of neochamaejasmin A (NCA), extracted from Stellera chamaejasme L., we first evaluated its cytotoxicity on the Spodoptera frugiperda (Sf9) cell line. The results confirmed that NCA inhibited Sf9 cell survival in both a dose- and time-dependent manner. Then, intracellular biochemical assays showed that NCA induced apoptosis in Sf9 cells. Evidence of apoptosis was confirmed by morphological changes and the activation of caspases-3/9. We also observed that NCA induced apoptosis via mitochondrial-dependent intrinsic apoptotic pathway by upregulating cytochrome c and proapoptotic protein (Bax) and downregulating the mitochondrial membrane potential (MMP) and antiapoptotic protein (Bcl-2). Moreover, we found a dose-dependent increase in reactive oxygen species (ROS), accumulation of lipid peroxidation product and an inactivation of the antioxidant enzymes in treated cells. Additionally, the cleavage of PARP and G2/M arrest were also detected in Sf9 cells exposed to NCA. These findings provide critical information that NCA effectively induced apoptosis in Sf9 cells through mitochondrial pathways.


Assuntos
Biflavonoides/química , Biflavonoides/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Thymelaeaceae/química , Animais , Apoptose/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Células Sf9 , Transdução de Sinais/efeitos dos fármacos , Spodoptera
4.
Chem Biodivers ; 16(7): e1900118, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31106521

RESUMO

In continuation of our previous research on the development of novel pyrazole-4-carboxamide with potential antifungal activity, compound SCU2028, namely N-[2-[(3-chlorophenyl)amino]phenyl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide, was synthesized by new method, structurally characterized by IR, HR-ESI-MS, 1 H- and 13 C-NMR spectra and further identified by single-crystal X-ray diffraction. In pot tests, compound SCU2028 showed good in vivo antifungal activity against Rhizoctonia solani (R. solani) and IC50 value of it was 7.48 mg L-1 . In field trials, control efficacy of compound SCU2028 at 200 g.a.i. ha-1 was 42.30 % on the 7th day after the first spraying and 68.10 % on the 14th day after the second spraying, only slightly lower than that of thifluzamide (57.20 % and 71.40 %, respectively). Further in vitro inhibitory activity showed inhibitory ability of compound SCU2028 was 45-fold higher than that of bixafen and molecular docking of compound SCU2028 to SDH predicted its binding orientation in the active site of the target protein SDH. These results suggested that compound SCU2028 was a potential fungicide for control of rice sheath blight.


Assuntos
Antifúngicos/farmacologia , Simulação de Acoplamento Molecular , Pirazóis/farmacologia , Rhizoctonia/efeitos dos fármacos , Antifúngicos/síntese química , Antifúngicos/química , Cristalografia por Raios X , Testes de Sensibilidade Microbiana , Estrutura Molecular , Pirazóis/síntese química , Pirazóis/química
5.
J Agric Food Chem ; 67(17): 5008-5016, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30977370

RESUMO

A series of novel N-(2-(phenylamino)-4-fluorophenyl)-pyrazole-4-carboxamides 1-15 and aromatic carboxamides with a diphenylamine scaffold 16-29 were designed, synthesized, and evaluated for their antifungal activities. In vitro experiments showed that compound 6 (EC50 = 0.03 mg/L) was superior to bixafen (EC50 = 0.04 mg/L) against Rhizoctoinia solani and compound 6 (IC50 = 1.41 mg/L) was close to bixafen (IC50 = 1.22 mg/L) against succinate dehydrogenase from R. solani. Additionally, in vivo pot experiments showed that compound 6 (EC50 = 1.93 mg/L) was better than bixafen (EC50 = 3.72 mg/L) and close to thifluzamide (EC50 = 1.83 mg/L) against R. solani. In vivo field trials showed that compound 6 at 200 g ai ha-1 had 64.10% control efficacy against rice sheath blight after 21 days with two sprayings, close to thifluzamide (71.40%). Furthermore, molecular docking showed that compound 6 anchors in the binding site of SDH.


Assuntos
Fungicidas Industriais/síntese química , Fungicidas Industriais/farmacologia , Difenilamina/química , Desenho de Drogas , Fungicidas Industriais/química , Simulação de Acoplamento Molecular , Estrutura Molecular , Oryza/microbiologia , Doenças das Plantas/microbiologia , Rhizoctonia/efeitos dos fármacos
6.
Bioorg Med Chem Lett ; 28(18): 3042-3045, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30097371

RESUMO

Sixteen novel pyrazole carboxamides with diarylamines scaffold were designed, synthesized and characterized in detail via 1H NMR, 13C NMR and ESI-HRMS. Preliminary bioassays showed that some of the target compounds exhibited good antifungal activity against Rhizoctonia solani, Fusarium oxysporum, Phytophthora infestans and Fusarium graminearum. Among them, compound 1c exhibited the highest antifungal activities against R. solani in vitro with EC50 value of 0.005 mg/L, superior to the commercially available fungicide fluxapyroxad (EC50 = 0.033 mg/L). And compound 1c (IC50 = 0.034 mg/L) showed higher inhibition abilities against succinate dehydrogenase than fluxapyroxad (IC50 = 0.037 mg/L). This study suggests that compound 1c could be regarded as a potential succinate dehydrogenase inhibitor.

7.
Bioorg Med Chem ; 26(9): 2280-2286, 2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29699910

RESUMO

Novel pyrazole carboxamides with a diarylamine-modified scaffold were modified based on the bixafen (Bayer) fungicide, which has excellent activity against Rhizoctonia solani, Rhizoctonia cerealis and Sclerotinia sclerotiorum. To discover the potential insecticidal activity of these novel pyrazole carboxamides, the present study explored their possible cytoactivity on the insect neuronal cells (RP-HzVNC-AW1) in Helicoverpa zea. The preliminary bioassays showed that some of the target compounds exhibited good cytoactivity against AW1 cells. Among them, compounds a5 and b4-b7 showed good activity in vitro with IC50 values of 11.28, 10.46, 9.04, 11.72 and 12.19 µM, respectively. Notably, the IC50 value of compound b5 was better than 11.81 µM for fipronil. We subsequently attempted to illustrate the mechanism of b5. Intracellular biochemical assays showed that b5 induced AW1 cell apoptosis with a decrease in themitochondrial membrane potential, as well as a significantly increased intracellular calcium ion concentration and caspase-3 activity. A significant decrease in Bcl-2 levels and a marked augmentation of cytochrome-c and Bax were also detected. These results indicate that a mitochondrially dependent intrinsic pathway contributes to compound b5-induced apoptosis in AW1 cells. This study suggests that b5 may act as a potential insecticide that can be used for further optimization.

8.
Bioorg Chem ; 73: 76-82, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28622596

RESUMO

Twelve novel fenfuram-diarylether hybrids were designed, synthesized and characterized by 1H NMR and MS. Their in vitro antifungal activities were evaluated against five phytopathogenic fungi by mycelial growth inhibition method. Most compounds showed significant antifungal effect on Rhizoctonia solani and Sclerotinia sclerotiorum. Compound 1c exhibited the most potent antifungal effect on R. solani with an EC50 value of 0.242mg/L, superior to the commercial fungicide boscalid (EC50=1.758mg/L) and the lead fungicide fenfuram (EC50=7.691mg/L). Molecular docking revealed that compound 1c featured a higher affinity for succinate dehydrogenase (SDH) than fenfuram. Furthermore, it was shown that the 2-chlorophenyl group of compound 1c formed a π-π stacking with D/Tyr-128 and a Cl-π interaction with B/His-249, which made compound 1c more active than fenfuram against SDH.


Assuntos
Antifúngicos/farmacologia , Inibidores Enzimáticos/farmacologia , Éteres/farmacologia , Furanos/farmacologia , Rhizoctonia/efeitos dos fármacos , Succinato Desidrogenase/antagonistas & inibidores , Antifúngicos/síntese química , Antifúngicos/química , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Éteres/química , Furanos/química , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Rhizoctonia/enzimologia , Relação Estrutura-Atividade , Succinato Desidrogenase/metabolismo
9.
Bioorg Med Chem Lett ; 27(1): 90-93, 2017 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-27884696

RESUMO

Ten novel fenfuram-diarylamine hybrids were designed and synthesized. And their antifungal activities against four phytopathogenic fungi have been evaluated in vitro and most of the compounds demonstrated a significant antifungal activities against Rhizoctonia solani and Sclerotinia sclerotiorum. Compound 5e exhibited the most potent antifungal activity against R. solani with an EC50 value of 0.037mg/L, far superior to the commercially available fungicide boscalid (EC50=1.71mg/L) and lead fungicide fenfuram (EC50=6.18mg/L). Furthermore, scanning electron microscopy images showed that the mycelia on treated media grew abnormally with tenuous, wizened and overlapping colonies compared to the negative control. Molecular docking studies revealed that compound 5e featured a higher affinity for succinate dehydrogenase (SDH) than fenfuram. Furthermore, it was shown that the 3-chlorophenyl group in compound 5e formed a CH-π interaction with B/Trp-206 and a Cl-π interaction with D/Tyr-128, rendering compound 5e more active than fenfuram against SDH.


Assuntos
Aminas/farmacologia , Antifúngicos/farmacologia , Ascomicetos/efeitos dos fármacos , Difenilamina/análogos & derivados , Desenho de Drogas , Furanos/farmacologia , Rhizoctonia/efeitos dos fármacos , Aminas/química , Antifúngicos/síntese química , Antifúngicos/química , Difenilamina/química , Difenilamina/farmacologia , Relação Dose-Resposta a Droga , Furanos/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade
10.
Springerplus ; 5(1): 1851, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27818889

RESUMO

BACKGROUND: In our previous studies, we discovered a series of chalcone-based phytopathogenic fungus inhibitors. However, knowledge of their effects, detailed targets and molecular mechanisms in Magnaporthe oryzae (M. oryzae) remained limited. METHODS: To explore the expression and function of differentially expressed genes in M. oryzae after treatment with compound C1, we analyzed the expression profile of mRNAs using a microarray analysis and GO, KEGG and WGCNA analysis, followed by qRT-PCR and Western blots to validate our findings. RESULTS: A total of 1013 up-regulated and 995 down-regulated mRNAs were differentially expressed after M. oryzae was treated with C1 compared to those of the control samples. Among these, cytochrome P450, glycylpeptide N-myristoyltransferase (NMT) and peroxisomal membrane protein 4 were identified as the most significant DEGs and were validated by experiments. CONCLUSION: In conclusion, our study suggests that the combination of transcriptomic microarray, bioinformatics analysis and weighted gene co-expression networks can be used to predict potential therapeutic targets and to map the pathways regulated by small molecular natural product-like drugs.

11.
Eur J Med Chem ; 120: 244-51, 2016 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-27191618

RESUMO

Twenty-seven novel furancarboxamide derivatives with a diphenyl ether moiety were synthesized and evaluated for their antifungal activity against Rhizoctonia solani, Botrytis cirerea, Valsa mali and Sphaceloma ampelimum. Antifungal bioassay results indicated that most compounds had good or excellent fungicidal activities for R. solani and S. ampelimum at 20 mg L(-1). Among synthesized compounds, compound 18e showed a greater inhibitory effect against S. ampelimum, with half maximal effective concentration (EC50) values of 0.020 mg L(-1). This strong activity rivals currently used commercial fungicides, such as Boscalid and Carbendazim, and has great potential as a lead compound for future development of novel fungicides.


Assuntos
Antifúngicos/síntese química , Furanos/farmacologia , Antifúngicos/farmacologia , Desenho de Drogas , Furanos/química , Testes de Sensibilidade Microbiana , Viabilidade Microbiana , Relação Estrutura-Atividade
12.
Prep Biochem Biotechnol ; 46(8): 747-754, 2016 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-26716611

RESUMO

A three-phase bed bioreactor including a mix of immobilized microbes was used to degrade isopropanol (IPA). The immobilization method was studied and cells immobilized with calcium alginate, polyvinyl alcohol, activated carbon, and SiO2 were demonstrated to be the best immobilization method for the degradation of 90% of 2 g/L IPA in just 4 days, 1 day earlier than with free cells. Acetone was monitored as an indicator of microbial IPA utilization as the major intermediate of aerobic IPA biodegradation. The bioreactor was operated at hydraulic retention time (HRT) values of 32, 24, 16, 12, and 10 hr, which correspond to membrane fluxes of 0.03, 0.04, 0.06, 0.08, and 0.10 L/m2/hr, respectively. The chemical oxygen demand (COD) removal efficiencies were maintained at 98.0, 97.8, 89.1, 80.6, and 71.1% at a HRT of 32, 24, 16, 12, and 10 hr, respectively, while the IPA degradations were 98.6, 98.3, 90.3, 81.6, and 73.3%, respectively. With a comprehensive consideration of COD removal and economy, the optimal HRT was 24 hr. The results demonstrate the potential of immobilized mixed bacterial consortium in a three-phase fluidized bed reactor system for the aerobic treatment of wastewater containing IPA.


Assuntos
2-Propanol/metabolismo , Reatores Biológicos , Poluentes Ambientais/metabolismo , Paracoccus denitrificans/metabolismo , Biodegradação Ambiental , Células Imobilizadas/metabolismo , Desenho de Equipamento
13.
Nat Prod Res ; 29(23): 2223-5, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25675117

RESUMO

We isolated Streptomyces sp. K15 from the root tissue of Houttuynia cordata Thunb and found that some of its secondary metabolites exhibited significant antimicrobial activity against Botrytis cinerea. Moreover, we separated, purified and identified the major active ingredient to be 2-pyrrol formic acid by using silica gel column chromatography, high-performance liquid chromatography and NMR analysis of the spectral data. 2-Pyrrol formic acid critically inhibited the growth of some phytopathogenic bacteria. Therefore, it has potential value in agricultural applications.


Assuntos
Anti-Infecciosos/química , Formiatos/química , Houttuynia/microbiologia , Pirróis/química , Streptomyces/química , Cromatografia Líquida de Alta Pressão , Endófitos/química , Formiatos/isolamento & purificação , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Estrutura Molecular , Pirróis/isolamento & purificação , Streptomyces/classificação
14.
Prep Biochem Biotechnol ; 45(5): 491-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-24840098

RESUMO

The biodegradation of high concentration isopropanol (2-propanol, IPA) at 16 g/L was investigated by a solvent-tolerant strain of bacteria identified as Paracoccus denitrificans for the first time by 16S rDNA gene sequencing. The strain P. denitrificans GH3 was able to utilize the high concentration of IPA as the sole carbon source within a minimal salts medium with a cell density of 1.5×10(8) cells/mL. The optimal conditions were found as follows: initial pH 7.0, incubation temperature 30°C, with IPA concentration 8 g/L. Under the optimal conditions, strain GH3 utilized 90.3% of IPA in 7 days. Acetone, the major intermediate of aerobic IPA biodegradation, was also monitored as an indicator of microbial IPA utilization. Both IPA and acetone were completely removed from the medium following 216 hr and 240 hr, respectively. The growth of strain GH3 on IPA as a sole carbon and energy source was well described by the Andrews model with a maximum growth rate (µmax)=0.0277/hr, a saturation constant (KS)=0.7333 g/L, and an inhibition concentration (Ki)=8.9887 g/L. Paracoccus denitrificans GH3 is considered to be well used in degrading IPA in wastewater.


Assuntos
2-Propanol/metabolismo , Paracoccus denitrificans/genética , Paracoccus denitrificans/metabolismo , Acetona/metabolismo , Biodegradação Ambiental , Meios de Cultura , Concentração de Íons de Hidrogênio , Cinética , Dados de Sequência Molecular , Paracoccus denitrificans/crescimento & desenvolvimento , Paracoccus denitrificans/isolamento & purificação , Filogenia , RNA Ribossômico 16S , Solventes/metabolismo , Temperatura Ambiente
15.
Can J Microbiol ; 59(5): 311-7, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23647343

RESUMO

The bacterial strain CC-5, isolated from contaminated soil and identified as Catellibacterium sp. based on morphology and partial 16S rDNA gene sequence analysis, utilized cypermethrin as its sole carbon source and degraded 97% of 100 mg·L(-1) cypermethrin within 7 days. The optimal degradation conditions were determined to be 30 °C and pH 7.0. Degradation was found to follow a first-order model at initial cypermethrin concentrations below 400 mg·L(-1). Strain CC-5 suffered substrate inhibition at high cypermethrin concentrations, and the biodegradation kinetics were successfully described by the Haldane model, with a maximal specific degradation rate of 1.36 day(-1), an inhibition constant of 164.61 mg·L(-1), and a half-saturation constant of 101.12 mg·L(-1). Inoculating cypermethrin-treated soil samples with strain CC-5 resulted in a higher rate of cypermethrin removal than that in noninoculated soil, regardless of whether the soil had previously been sterilized. These results reveal that the bacterial strain may possess potential to be used in bioremediation of pyrethroid-contaminated environment.


Assuntos
Piretrinas/metabolismo , Rhodobacteraceae/isolamento & purificação , Rhodobacteraceae/metabolismo , Microbiologia do Solo , Poluentes do Solo/metabolismo , Biodegradação Ambiental , DNA Ribossômico/genética , Rhodobacteraceae/classificação
16.
J Gen Appl Microbiol ; 58(4): 263-71, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22990486

RESUMO

A bacterial strain named CB4, with highly effective glyphosate degradation capability, was isolated from soil after enrichment. On the basis of the Biolog omniLog identification system (Biolog) and 16S ribosomal RNA (rRNA) gene sequencing methods, strain CB4 was identified as Bacillus cereus. Further experiments were carried out to optimize the growth of strain CB4 and the glyphosate degradation activity by high performance liquid chromatography (HPLC). The optimal conditions were found as follows: initial pH 6.0, incubation temperature 35°C, glyphosate concentration 6 g L(-1), inoculation amount 5% and incubation time 5 days. Under the optimal conditions, stain CB4 utilized 94.47% of glyphosate. This is the first report on B. cereus with a capacity to utilize herbicide glyphosate, and it can degrade glyphosate concentrations up to 12 g L(-1). Metabolization of glyphosate by strain B. cereus CB4 was studied. Results indicated that two concurrent pathways were capable of degrading glyphosate to AMPA, glyoxylate, sarcosine, glycine and formaldehyde as products. Glyphosate breakdown in B. cereus CB4 was achieved by the C-P lyase activity and the glyphosate oxidoreductase activity.


Assuntos
Bacillus cereus/classificação , Bacillus cereus/isolamento & purificação , Glicina/análogos & derivados , Herbicidas/metabolismo , Microbiologia do Solo , Bacillus cereus/genética , Bacillus cereus/metabolismo , Técnicas de Tipagem Bacteriana , Biotransformação , Cromatografia Líquida de Alta Pressão , Análise por Conglomerados , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Glicina/metabolismo , Concentração de Íons de Hidrogênio , Dados de Sequência Molecular , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Temperatura Ambiente
17.
Toxicol Mech Methods ; 22(4): 315-20, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22339240

RESUMO

The objective of this study was to examine the toxicity of 1-(4-morpholinophenyl)-3-(4-fluorophenyl)-propenone (A) and 1-(4-morpholinophenyl)-3-(3-fluorophenyl)-propenone (B) on Spodoptera frugiperda (Sf9) cells and the mechanism of the toxicity. By cell-based thiazolyl blue tetrazolium bromide (MTT) assay, we found that the IC(50) were 35.45 µM for A and 31.97 µM for B respectively. Formation of apoptotic bodies was observed at 24 h in the treated cells. There was a significant increase of DNA ladders in the treated Sf9 cells compared to controls. In the presence of 50 µM compound A and B for 24 h, ATP content of Sf9 cells reduced by approximately 50%. Compared to the controls, the significant over-expression of caspase-3 in treated cells was measured by caspase-3 activity kit, and the loss of mitochondrial membrane potential (ΔΨm) was detected in apoptosis cells. The results suggested that the two compounds could be identified as new potent cell apoptosis inducers.


Assuntos
Apoptose/efeitos dos fármacos , Morfolinas/toxicidade , Trifosfato de Adenosina/metabolismo , Animais , Caspase 3/metabolismo , Linhagem Celular , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estrutura Molecular , Spodoptera
18.
Chem Biol Drug Des ; 79(3): 279-89, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22181692

RESUMO

Pyrazolines, the well-known five-membered nitrogen-containing heterocyclic compounds, have received considerable interests in the fields of medicinal and agricultural chemistry because of their broad spectrum of biological activities. To discover more potent antifungal compounds, a series of structurally related 1,3,5-trisubstituted-2-pyrazoline derivatives have been synthesized by introducing furan rings regarded as bioactive substructure into the scaffold of pyrazolines and tested for their activities against six plant pathogenic fungi in vitro. The preliminary bioassays indicated that almost all synthesized compounds had displayed variable growth inhibitory effects on the tested pathogenic fungi. In particular, compounds 4, 7, 9, 12, 18, 19, and 38 displayed excellent antifungal activities against Rhizoctonia solani and their inhibition of growth reached 100% at the concentration of 20 mg/L. Additionally, compounds 9 and 19 bearing two furan rings, respectively, at site 3 and site 5 of the pyrazoline cycle showed the strongest activities against R. solani (the EC(50) were 3.46 mg/L and 3.20 mg/L). The bioactivity results provide good starting templates for further structural optimization of pyrazoline derivatives.


Assuntos
Antifúngicos/síntese química , Antifúngicos/farmacologia , Fungos/efeitos dos fármacos , Pirazóis/química , Pirazóis/farmacologia , Antifúngicos/química , Furanos/química , Testes de Sensibilidade Microbiana , Pirazóis/síntese química , Relação Estrutura-Atividade
19.
Folia Microbiol (Praha) ; 56(6): 555-61, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22083789

RESUMO

Neomycin, produced by Streptomyces fradiae, has been widely used for the treatment of bacterial infections in clinical and agricultural applications. In this study, a neomycin nonproducing mutant of S. fradiae was obtained by gene disruption technique for mutational biosynthesis. A crucial gene neoC (neo7) which encodes 2-deoxystreptamine (2-DOS) synthases was disrupted. The mutant could resume producing neomycin in the presence of 2-DOS. Salen derivatives of 2-DOS were synthesized and individually added to cultures of the mutant. Antibacterial activity of the mutasynthesis products against Staphylococcus aureus and four plant pathogenic bacteria (Pseudomonas solanacarum, Erwinia carotovora, Xanthomonas oryzae, and Xanthomonas campestris) was detected quantitatively by Oxford cup method. It is suggested that all 2-DOS derivatives were incorporated by the mutant into new active neomycin analogs except for 2-DOS derivative 2d ((1R,2r,3S,4R,6S)-4,6-bis((E)-3,5-di-tert-butyl-2-hydroxybenzylideneamino)cyclohexane-1,2,3-triol). Neomycin analogs produced by feeding 2-DOS derivative 2a ((1R,2r,3S,4R,6S)-4,6-bis((E)-2 hydroxybenzylideneamino)cyclohexane-1,2,3-triol) to cultures of the mutant displayed a similar antibacterial activity with neomycin produced by wild strain.


Assuntos
Antibacterianos/biossíntese , Neomicina/biossíntese , Streptomyces/genética , Streptomyces/metabolismo , Antibacterianos/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Estrutura Molecular , Mutação , Neomicina/análogos & derivados , Streptomyces/enzimologia
20.
Chem Biol Drug Des ; 78(1): 94-100, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21457470

RESUMO

Three natural products, 1,5-diphenylpentan-1-one, 1,5-diphenylpent-2-en-1-one, and 3-hydroxy-1,5-diphenylpentan-1-one, with good insecticidal activities were extracted from Stellera chamaejasme L. Based on their shared diaryl ketone moiety as 'pharmacophores', a series of diaryl ketones were synthesized and tested for insecticidal activity, acetylcholinesterase inhibitory activity, and antifungal activity. All synthesized compounds showed poor insecticidal and acetylcholinesterase inhibitory activities. Compound III with a furyl ring showed strong activities against plant pathogenic fungi. The IC(50) of compound (E)-1-(2,4-dichlorophenyl)-3-(furan-2-yl)- -prop-2-en-1-one (III(2) ) was 1.20 mg/L against Rhizoctonia solani, suggesting its strong potential as a novel antifungal drug.


Assuntos
Produtos Biológicos/isolamento & purificação , Cetonas/química , Praguicidas/química , Praguicidas/farmacologia , Animais , Antifúngicos/síntese química , Antifúngicos/química , Antifúngicos/farmacologia , Afídeos , Inibidores da Colinesterase/farmacologia , Avaliação Pré-Clínica de Medicamentos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Praguicidas/síntese química
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