Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 271
Filtrar
1.
Molecules ; 26(6)2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33803890

RESUMO

A series of novel nopol derivatives bearing the 1,3,4-thiadiazole-thiourea moiety were designed and synthesized by multi-step reactions in search of potent natural product-based antifungal agents. Their structures were confirmed by FT-IR, NMR, ESI-MS, and elemental analysis. Antifungal activity of the target compounds was preliminarily evaluated by in vitro methods against Fusarium oxysporum f. sp. cucumerinum, Cercospora arachidicola, Physalospora piricola, Alternaria solani, Gibberella zeae, Rhizoeotnia solani, Bipolaris maydis, and Colleterichum orbicalare at 50 µg/mL. All the target compounds exhibited better antifungal activity against P. piricola, C. arachidicola, and A. solani. Compound 6j (R = m, p-Cl Ph) showed the best broad-spectrum antifungal activity against all the tested fungi. Compounds 6c (R = m-Me Ph), 6q (R = i-Pr), and 6i (R = p-Cl Ph) had inhibition rates of 86.1%, 86.1%, and 80.2%, respectively, against P. piricola, much better than that of the positive control chlorothalonil. Moreover, compounds 6h (R = m-Cl Ph) and 6n (R = o-CF3 Ph) held inhibition rates of 80.6% and 79.0% against C. arachidicola and G. zeae, respectively, much better than that of the commercial fungicide chlorothalonil. In order to design more effective antifungal compounds against A. solani, analysis of the three-dimensional quantitative structure-activity relationship (3D-QSAR) was carried out using the CoMFA method, and a reasonable and effective 3D-QSAR model (r2 = 0.992, q2 = 0.753) has been established. Furthermore, some intriguing structure-activity relationships were found and are discussed by theoretical calculation.


Assuntos
Antifúngicos/síntese química , Antifúngicos/farmacologia , Compostos Bicíclicos com Pontes/farmacologia , Tiadiazóis/farmacologia , Tioureia/análogos & derivados , Antifúngicos/química , Compostos Bicíclicos com Pontes/química , Desenho de Fármacos , Fungos/efeitos dos fármacos , Fungicidas Industriais/síntese química , Fungicidas Industriais/química , Fungicidas Industriais/farmacologia , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Relação Quantitativa Estrutura-Atividade , Eletricidade Estática , Tiadiazóis/química , Tioureia/química , Tioureia/farmacocinética
2.
Int J Mol Sci ; 22(7)2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33918510

RESUMO

The increasing emergence of fungicide-resistant pathogens requires urgent solutions for crop disease management. Here, we describe a structural investigation of new fungicides obtained by combining strobilurin and succinate dehydrogenase inhibitor pharmacophores. We identified compounds endowed with very good activity against wild-type Pyricularia oryzae, combined in some cases with promising activity against strobilurin-resistant strains. The first three-dimensional model of P. oryzae cytochrome bc1 complex containing azoxystrobin as a ligand was developed. The model was validated with a set of commercially available strobilurins, and it well explains both the resistance mechanism to strobilurins mediated by the mutation G143A and the activity of metyltetraprole against strobilurin-resistant strains. The obtained results shed light on the key recognition determinants of strobilurin-like derivatives in the cytochrome bc1 active site and will guide the further rational design of new fungicides able to overcome resistance caused by G143A mutation in the rice blast pathogen.


Assuntos
Ascomicetos , Farmacorresistência Fúngica , Fungicidas Industriais/síntese química , Estrobilurinas/química , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Succinato Desidrogenase/antagonistas & inibidores
3.
Carbohydr Polym ; 261: 117821, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33766331

RESUMO

Damage to the cell membrane is an effective method to prevent drug resistance in plant fungal diseases. Here, we proposed a negative remodeling model of the cell membrane structure induced by the C-coordinated O-carboxymethyl chitosan Cu (II) complex (O-CSLn-Cu). FITC-labeled O-CSLn-Cu (FITC-O-CSLn-Cu) was first synthesized via a nucleophilic substitution reaction and confirmed by FT-IR. FITC-labeled O-CSLn-Cu could pass through the fungal cell membrane, as detected by confocal laser scanning microscopy (CLSM) coupled with fluorescein isothiocyanate (FITC)-fluorescence. O-CSLn-Cu treatment led to apparent morphological changes in the membranes of P. capsici Leonian and giant unilamellar vesicles (GUVs) by transmission electron microscopy (TEM). Then, we performed component analysis of the cell membrane from the P. capsici Leonian affected by O-CSLn-Cu with a particular interest in membrane physicochemical properties. Many unsaturated fatty acids (UFAs) and key enzymes promoting UFA synthesis of the cell membrane were downregulated. Similarly, a large number of membrane proteins responsible for substance transport and biochemical reactions were downregulated. Furthermore, O-CSLn-Cu treatments increased plasma membrane permeability with significant leakage of intercellular electrolytes, soluble proteins and sugars, and lipid peroxidation with decreasing membrane fluidity. Finally, aquaporin 10 was proven to be a potential molecular target sensitive to antimicrobial agents according to composition analysis of membrane structure and immunohistochemistry.


Assuntos
Antifúngicos/farmacologia , Permeabilidade da Membrana Celular/efeitos dos fármacos , Quitosana/análogos & derivados , Cobre/química , Phytophthora/efeitos dos fármacos , Animais , Antifúngicos/síntese química , Antifúngicos/química , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Quitosana/química , Quitosana/farmacologia , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Cobre/farmacologia , Fungicidas Industriais/síntese química , Fungicidas Industriais/química , Fungicidas Industriais/farmacologia , Fluidez de Membrana/efeitos dos fármacos , Lipídeos de Membrana/fisiologia , Phytophthora/metabolismo , Phytophthora/ultraestrutura , Coelhos , Esporos/efeitos dos fármacos , Esporos/fisiologia
4.
Carbohydr Polym ; 261: 117904, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33766382

RESUMO

Chitosan, a low-cost and multipurpose polymer with numerous desired physicochemical and biological properties has been tested for various applications in agriculture, pharmacy, and biomedicine industries. The availability of functional groups along the backbone makes chitosan readily available for other polymers and metal ions to form bio-nanocomposites. Different types of chitosan-based nanocomposites have been designed and tested for the enhancement of chitosan efficiency and ultimately widening the application areas of chitosan in plants. These nanocomposites serve different purposes such as eliciting plant's defence systems against different threats (pathogen attack), antimicrobial agent against bacteria, fungi and viruses, enhancement of nutrient uptake by plants, control release of micro/macronutrients, fungicides and herbicides. In this review, an extensive outlook has been provided (mainly in the last five years) to recent trends and advances in the fabrication and application of chitosan-based composites. Finally, current challenges and future development opportunities of chitosan-based nanocomposites for plants are discussed.


Assuntos
Química Agrícola/tendências , Quitosana/química , Fungicidas Industriais/síntese química , Nanocompostos , Doenças das Plantas/prevenção & controle , Agricultura/métodos , Agricultura/tendências , Química Agrícola/métodos , Fungicidas Industriais/química , Humanos , Nanocompostos/química , Nanocompostos/uso terapêutico
5.
J Agric Food Chem ; 69(3): 945-954, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33438400

RESUMO

A novel chemical conjugate between chitosan (CH) and riboflavin (RF) has been synthesized and characterized via Fourier transform infrared, NMR, and other spectroscopic methods. Photophysical and photochemical properties such as absorption spectra, fluorescence emission, fluorescence anisotropy, and singlet oxygen generation were characterized as well. This new biopolymer-based conjugate was designed to have an antifungal effect enhanced through antimicrobial photodynamic therapy. The antifungal effect of this conjugate (CH-RF) was compared with CH and RF against Penicillium digitatum in vitro. The conjugate showed the highest fungal growth inhibition of all systems tested at a dose of 0.5% w/v. This new biopolymer-based compound could be a promising alternative to fungicides used in citrus fruits postharvest.


Assuntos
Quitosana/química , Quitosana/farmacologia , Fungicidas Industriais/farmacologia , Penicillium/efeitos dos fármacos , Riboflavina/química , Riboflavina/farmacologia , Citrus/microbiologia , Fungicidas Industriais/síntese química , Fungicidas Industriais/química , Luz , Penicillium/crescimento & desenvolvimento , Doenças das Plantas/microbiologia
6.
J Agric Food Chem ; 69(4): 1214-1223, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33480684

RESUMO

A series of new fungicides that can inhibit the succinate dehydrogenase (SDH) was classified and named as SDH inhibitors by the Fungicide Resistance Action Committee in 2009. To develop more potential SDH inhibitors, we designed and synthesized a novel series of N-(substituted pyridine-4-yl)-1-(substituted phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide derivatives, 4a-4i, namely, 5a-5h, 6a-6h, and 7a-7j. The bioassay results demonstrated that some title compounds exhibited excellent antifungal activity against four tested phytopathogenic fungi (Gibberella zea, Fusarium oxysporum, Cytospora mandshurica, and Phytophthora infestans). The EC50 values were 1.8 µg/mL for 7a against G. zeae, 1.5 and 3.6 µg/mL for 7c against F. oxysporum and C. mandshurica, respectively, and 6.8 µg/mL for 7f against P. infestans. The SDH enzymatic activity testing revealed that the IC50 values of 4c, 5f, 7f, and penthiopyrad were 12.5, 135.3, 6.9, and 223.9 µg/mL, respectively. The molecular docking results of this series of title compounds with SDH model demonstrated that the compounds could completely locate inside of the pocket, the body fragment formed H bonds, and the phenyl ring showed a π-π interaction with Arg59, suggesting that these novel 5-trifluoromethyl-pyrazole-4-carboxamide derivatives might target SDH. These results could provide a benchmark for understanding the antifungal activity against the phytopathogenic fungus P. infestans and prompt us to discover more potent SDH inhibitors.


Assuntos
Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Proteínas Fúngicas/antagonistas & inibidores , Fungicidas Industriais/química , Fungicidas Industriais/farmacologia , Pirazóis/química , Pirazóis/farmacologia , Succinato Desidrogenase/antagonistas & inibidores , Inibidores Enzimáticos/síntese química , Proteínas Fúngicas/química , Fungicidas Industriais/síntese química , Fusarium/efeitos dos fármacos , Fusarium/enzimologia , Simulação de Acoplamento Molecular , Relação Quantitativa Estrutura-Atividade , Succinato Desidrogenase/química
7.
J Agric Food Chem ; 69(4): 1224-1233, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33480687

RESUMO

To further study the structure-activity relationship of gossypol, hemigossypol (1) and its derivatives (2-23) were successfully designed via structure simplification and chemically synthesized. The anti-tobacco mosaic virus (TMV), fungicidal, and insecticidal activities of them were tested systematically. Most of these derivatives exhibited excellent anti-TMV activity. Furthermore, these compounds also exhibited broad-spectrum fungicidal activities against 14 kinds of phytopathogenic fungi. In particular, hemigossypol acid lactone (7) was stable in the air. In terms of biological activity, it not only showed anti-TMV activity (inhibitory rates of 70.3, 65.4 and 72.4% at 500 µg/mL for inactivation, curative, and protection activity in vivo, respectively) comparable to ningnanmycin but also exhibited higher insecticidal activity against mosquito larvae (60%/0.25 mg/kg) than the commercial species rotenone. None of hemigossypol and the tested derivatives showed antitumor activities.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Antivirais/síntese química , Antivirais/farmacologia , Fungicidas Industriais/síntese química , Fungicidas Industriais/farmacologia , Inseticidas/síntese química , Inseticidas/farmacologia , Animais , Antineoplásicos/química , Antivirais/química , Produtos Biológicos/síntese química , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Linhagem Celular Tumoral , Culicidae/efeitos dos fármacos , Culicidae/crescimento & desenvolvimento , Desenho de Fármacos , Fungos/efeitos dos fármacos , Fungos/crescimento & desenvolvimento , Fungicidas Industriais/química , Gossipol/química , Gossipol/farmacologia , Humanos , Inseticidas/química , Doenças das Plantas/microbiologia , Doenças das Plantas/virologia , Relação Estrutura-Atividade , Vírus do Mosaico do Tabaco/efeitos dos fármacos
8.
J Agric Food Chem ; 69(4): 1259-1271, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33496176

RESUMO

Inspired by the widely antiphytopathogenic application of diversified derivatives from natural sources, cryptolepine and its derivatives were subsequently designed, synthesized, and evaluated for their antifungal activities against four agriculturally important fungi Rhizoctonia solani, Botrytis cinerea, Fusarium graminearum, and Sclerotinia sclerotiorum. The results obtained from in vitro assay indicated that compounds a1-a24 showed great fungicidal property against B. cinerea (EC50 < 4 µg/mL); especially, a3 presented significantly prominent inhibitory activity with an EC50 of 0.027 µg/mL. In the pursuit of further expanding the antifungal spectrum of cryptolepine, ring-opened compound f1 produced better activity with an EC50 of 3.632 µg/mL against R. solani and an EC50 of 5.599 µg/mL against F. graminearum. Furthermore, a3 was selected to be a candidate to investigate its preliminary antifungal mechanism to B. cinerea, revealing that not only spore germination was effectively inhibited and the normal physiological structure of mycelium was severely undermined but also detrimental reactive oxygen was obviously accumulated and the normal function of the nucleus was fairly disordered. Besides, in vivo curative experiment against B. cinerea found that the therapeutic action of a3 was comparable to that of the positive control azoxystrobin. These results suggested that compound a3 could be regarded as a novel and promising agent against B. cinerea for its valuable potency.


Assuntos
Fungicidas Industriais/síntese química , Fungicidas Industriais/farmacologia , Alcaloides Indólicos/química , Alcaloides Indólicos/farmacologia , Quinolinas/química , Quinolinas/farmacologia , Ascomicetos/efeitos dos fármacos , Ascomicetos/crescimento & desenvolvimento , Desenho de Fármacos , Fungicidas Industriais/química , Fusarium/efeitos dos fármacos , Fusarium/crescimento & desenvolvimento , Doenças das Plantas/microbiologia , Rhizoctonia/efeitos dos fármacos , Rhizoctonia/crescimento & desenvolvimento , Relação Estrutura-Atividade
9.
Eur J Med Chem ; 210: 113048, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33316690

RESUMO

Invasive candidiasis, such as intra-abdominal candidiasis (IAC), is a significant cause of morbidity and mortality worldwide. IAC is still poorly understood, and its treatment represents a challenge for public health. In this study, we showed the in vitro anti-Candida activity of four alkaloid synthetic derivatives and their antifungal potential in a murine model of IAC. The biological effects of alkaloids were evaluated against Candida spp. through the determination of the minimum inhibitory concentration (MIC). For the alkaloids that showed antifungal activity, the fungicidal concentration, time-kill curve, synergism with azoles and polyenes, phenotypic effects, and the effect against virulence factors were also determined. The most active alkaloids were selected for in vivo assays. The compounds 6a and 6b were active against C. albicans, C. glabrata, and C. tropicalis (MIC 7.8 µg/mL) and showed promising antifungal activity against C. krusei (MIC 3.9 µg/mL). The compound 6a presented a potent fungicidal effect in vitro, eliminating the yeast C. albicans after 8 h of incubation at MIC. An important in vitro synergistic effect with ketoconazole was observed for these two alkaloids. They also induced the lysis of fungal cells by binding to the ergosterol of the membrane. Besides that, 6a and 6b were able to reduce yeast-to-hyphal transition in C. albicans, as well as inhibit the biofilm formation of this pathogen. In the in vivo assay, the compound 6a did not show acute toxicity and was mainly absorbed by the liver, spleen, and lung after a parenteral administration. Also, this analogue significantly reduced the fungal load of C. albicans on the kidney and spleen of animals with IAC. Therefore, these results showed that the compound 6a is a potent anti-Candida agent in vitro and in vivo.


Assuntos
Alcaloides/farmacologia , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Desenho de Fármacos , Fungicidas Industriais/farmacologia , Alcaloides/síntese química , Alcaloides/química , Antifúngicos/síntese química , Antifúngicos/química , Relação Dose-Resposta a Droga , Fungicidas Industriais/síntese química , Fungicidas Industriais/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade
10.
Eur J Med Chem ; 194: 112253, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32222678

RESUMO

The prevention and control of plant diseases and insect pests is the most crucial issue facing crop protection. To discover novel pesticide candidates with diverse chemical structures from natural products, a series of luotonin A analogues were designed, synthesized and evaluated for their antifungal and insecticidal activities. Most of these compounds exhibited potent activity against Botrytis cinerea, Magnaporthe oryzae and Aphis craccivora. Among them, the antifungal activity of compound 10s against B. cinerea was comparable to azoxystrobin (EC50 = 0.09 mM) and against M. oryzae (EC50 = 0.19 mM) was slightly weaker than that of azoxystrobin (EC50 = 0.17 mM). Compounds 10k and 10o are the most active compounds against A. craccivora having identical mortality value of 42.05% at 50 µg/mL, respectively, which were slightly lower than pymetrozine (51.14%) at the same concentration. Revealed morphological changes of the fungal cell surface by scanning electron microscopy indicated that luotonin A analogues might exert their antifungal activity by destroying fungal cell membrane and cell wall. Furthermore, the results of the in vivo protective and curative activities of the compound 10s against S. sclerotiorum and B. cinerea showed that the curative effect was stronger than its protective effect and the curative effects reached 67.17% and 73.82% at 80 µg/mL respectively. The above results further demonstrated the potential of luotonin A analogues as novel fungicides and insecticides.


Assuntos
Alcaloides/farmacologia , Produtos Biológicos/farmacologia , Descoberta de Drogas , Fungicidas Industriais/farmacologia , Inseticidas/farmacologia , Pirróis/farmacologia , Quinonas/farmacologia , Alcaloides/síntese química , Alcaloides/química , Animais , Afídeos/efeitos dos fármacos , Produtos Biológicos/síntese química , Produtos Biológicos/química , Botrytis/efeitos dos fármacos , Relação Dose-Resposta a Droga , Fungicidas Industriais/síntese química , Fungicidas Industriais/química , Inseticidas/síntese química , Inseticidas/química , Magnaporthe/efeitos dos fármacos , Estrutura Molecular , Pirróis/síntese química , Pirróis/química , Quinonas/síntese química , Quinonas/química , Relação Estrutura-Atividade
11.
J Agric Food Chem ; 68(8): 2306-2315, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-31995378

RESUMO

Neocryptolepine is an alkaloid isolated from traditional African herbal medicine Cryptolepis sanguinolenta, and its broad spectrum of biological activities has been illuminated in past decades. In this study, neocryptolepine and its derivatives (1-49) were designed and synthesized from economical and readily available starting materials. Their structures were confirmed by proton nuclear magnetic resonance, carbon nuclear magnetic resonance, and mass spectrometry. The synthesized compounds were screened for their antifungal profile against six agriculturally important fungi Rhizoctonia solani, Botrytis cinerea (B. cinerea), Fusarium graminearum, Mycosphaerella melonis, Sclerotinia sclerotiorum, and Magnaporthe oryzae. The results of in vitro assay revealed that compounds 5, 21, 24, 35, 40, 45, and 47 presented remarkable antifungal activity against the fungi tested with EC50 values lower than 1 µg/mL. Significantly, compound 24 displayed the most effective inhibitory potency against B. cinerea (EC50 = 0.07 µg/mL), and the data from in vivo experiments revealed that compound 24 demonstrated comparable protective activity with the positive control boscalid. Preliminary mechanism studies indicated that compound 24 showed impressive spore germination inhibitory effectiveness and lower cytotoxicity than azoxystrobin, imparted on normal function of the cell membrane and cell wall, and arrested the normal function of the nucleus. Besides the excellent inhibitory activity against agriculturally important phytopathogenic fungi tested, the designed assemblage possesses several benefits with a high profile of variation in synthesized molecules, the ease of synthesis, and good cost-effectiveness of commercially available synthetic reagents, all of these have highlighted the potential worth of compound 24 as a new and highly efficient agricultural fungicide.


Assuntos
Antifúngicos/farmacologia , Fungicidas Industriais/farmacologia , Doenças das Plantas/microbiologia , Antifúngicos/síntese química , Antifúngicos/química , Botrytis/efeitos dos fármacos , Botrytis/crescimento & desenvolvimento , Fungicidas Industriais/síntese química , Fungicidas Industriais/química , Fusarium/efeitos dos fármacos , Fusarium/crescimento & desenvolvimento , Estrutura Molecular , Rhizoctonia/efeitos dos fármacos , Rhizoctonia/crescimento & desenvolvimento , Relação Estrutura-Atividade
12.
J Agric Food Chem ; 68(7): 2116-2123, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-31986045

RESUMO

Fungal pathogens cause serious crop diseases and decrease crop yields and quality. Polyacetylene alcohols are plant secondary metabolites and bioactive against various pathogenic fungi. They are, however, difficult to synthesize. In the present study, an efficient and highly enantioselective method (>98% ee) was established and employed to achieve the synthesis of the natural C18 polyacetylenes (S,E)-octadeca-1,9-dien-4,6-diyn-3-ol 1, (3R,10R,E)-octadeca-1,8-dien-4,6-diyne-3,10-diol 2, and their analogs. The title compounds were structurally characterized and biologically evaluated for fungicidal activities. The compounds exhibited high potencies against eight pathogenic fungal species tested, such as Colletotrichum gloeosporioiles, Bipolaris sorokiniana, Fusarium graminearum, and Fusarium pseudograminearum, with half-maximum effective concentrations ranging from 8 to 425 µg/mL, being similar to those of the fungicide thiophanate-methyl (3-408 µg/mL). These compounds are potential natural fungicides and fungicide lead candidates for further structural and property improvements.


Assuntos
Fungicidas Industriais/química , Fungicidas Industriais/farmacologia , Polímero Poliacetilênico/química , Polímero Poliacetilênico/farmacologia , Colletotrichum/efeitos dos fármacos , Colletotrichum/crescimento & desenvolvimento , Fungicidas Industriais/síntese química , Fusarium/efeitos dos fármacos , Fusarium/crescimento & desenvolvimento , Doenças das Plantas/microbiologia , Polímero Poliacetilênico/síntese química , Estereoisomerismo
13.
Chemistry ; 26(21): 4734-4751, 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-31774931

RESUMO

The catalyst H3+x PMo12-x +6 Mox +5 O40 supported on SiO2 was developed for peroxidation of 1,3- and 1,5-diketones with hydrogen peroxide with the formation of bridged 1,2,4,5-tetraoxanes and bridged 1,2,4-trioxolanes (ozonides) with high yield based on isolated products (up to 86 and 90 %, respectively) under heterogeneous conditions. Synthesis of peroxides under heterogeneous conditions is a rare process and represents a challenge for this field of chemistry, because peroxides tend to decompose on the surface of a catalyst . A new class of antifungal agents for crop protection, that is, cyclic peroxides: bridged 1,2,4,5-tetraoxanes and bridged ozonides, was discovered. Some ozonides and tetraoxanes exhibit a very high antifungal activity and are superior to commercial fungicides, such as Triadimefon and Kresoxim-methyl. It is important to note that none of the fungicides used in agricultural chemistry contains a peroxide fragment.


Assuntos
Fungicidas Industriais/química , Compostos Heterocíclicos/química , Peróxido de Hidrogênio/química , Cetonas/química , Peróxidos/síntese química , Dióxido de Silício/química , Tetraoxanos/síntese química , Catálise , Fungicidas Industriais/síntese química , Peróxidos/química , Tetraoxanos/química
14.
J Agric Food Chem ; 67(50): 13904-13913, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31765135

RESUMO

A series of N-aryl-pyridine-4-one derivatives were designed and synthesized using maltol and antidesmone as lead compounds, and then their fungicidal/bactericidal activities and possible mechanism of action against Colletotrichum musae were explored. Most of these compounds exhibited significant fungicidal activity in vitro. Especially, compound 23 has more than 90% inhibitory activity against nine plant pathogenic fungi at 50 µg mL-1, which is superior to azoxystrobin. Moreover, an in vivo bioassay also demonstrated that compound 23 exhibited high-efficiency broad-spectrum antifungal activity and can effectively control postharvest diseases of mango. In addition, it was found that compounds 22 and 23 can also effectively control rice bacterial leaf blight in pot experiments, which was even more effective than zhongshengmycin. Preliminary mechanism studies revealed that compound 23 may cause cell membrane and mitochondria destruction. These findings indicate that compound 23 can be used to develop potential agrochemical fungicides and bactericides.


Assuntos
Agroquímicos/química , Agroquímicos/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Fungicidas Industriais/química , Fungicidas Industriais/farmacologia , Agroquímicos/síntese química , Colletotrichum/efeitos dos fármacos , Fungicidas Industriais/síntese química , Mangifera/microbiologia , Estrutura Molecular , Oryza/microbiologia , Doenças das Plantas/microbiologia , Piridinas/química , Piridinas/farmacologia , Rhizoctonia , Relação Estrutura-Atividade , Xanthomonas/efeitos dos fármacos , Xanthomonas/crescimento & desenvolvimento
15.
J Agric Food Chem ; 67(47): 13185-13194, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31697490

RESUMO

In searching for novel fungicidal leads, the novel bioactive succinate dehydrogenase inhibitor (SDHI) derivatives were designed and synthesized by the inversion of carbonyl and amide groups. Bioassay indicated that compound 5i stood out with a broad spectrum of in vitro activity against five fungi. Its EC50 value (0.73 µg/mL) was comparable to that of boscalid (EC50 of 0.51 µg/mL) and fluxapyroxad (EC50 of 0.19 µg/mL) against Sclerotinia sclerotiorum. For Rhizoctonia cerealis, 5i and 5p with EC50 values of 4.61 and 6.48 µg/mL, respectively, showed significantly higher activity than fluxapyroxad with the EC50 value of 16.99 µg/mL. In vivo fungicidal activity of 5i exhibited an excellent inhibitory rate (100%) against Puccinia sorghi at 50 µg/mL, while the positive control boscalid showed only a 70% inhibitory rate. Moreover, 5i showed promising fungicidal activity with a 60% inhibitory rate against Rhizoctonia solani at 1 µg/mL, which was better than that of boscalid (30%). Compound 5i possessed better in vivo efficacy against P. sorghi and R. solani than boscalid. Molecular docking showed that even the carbonyl oxygen atom of 5i was far from the pyrazole ring. It could also form hydrogen bonds toward the hydroxyl hydrogen and amino hydrogen of TYR58 and TRP173 on SDH, respectively, which consisted of the positive control fluxapyroxad. Fluorescence quenching analysis and SDH enzymatic inhibition studies also validated its mode of action. Our studies showed that 5i was worthy of further investigation as a promising fungicide candidate.


Assuntos
Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Proteínas Fúngicas/antagonistas & inibidores , Fungicidas Industriais/síntese química , Fungicidas Industriais/farmacologia , Succinato Desidrogenase/antagonistas & inibidores , Ascomicetos/química , Ascomicetos/efeitos dos fármacos , Ascomicetos/enzimologia , Inibidores Enzimáticos/química , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Fungicidas Industriais/química , Simulação de Acoplamento Molecular , Rhizoctonia/química , Rhizoctonia/efeitos dos fármacos , Rhizoctonia/enzimologia , Relação Estrutura-Atividade , Succinato Desidrogenase/química , Succinato Desidrogenase/metabolismo
16.
J Agric Food Chem ; 67(45): 12357-12365, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31596575

RESUMO

A series of isothiazole, 1,2,3-thiadiazole, and thiazole-based cinnamamide morpholine derivatives were rationally designed, synthesized, characterized, and evaluated for their fungicidal activities. Bioassay indicated that a combination of 3,4-dichloroisothiazole active substructures with cinnamamide morpholine lead to significant improvement of in vivo antifungal activities of the target compounds; among them, compound 5a exhibited good fungicidal activity against Pseudoperonspera cubensis in vivo with an inhibition rate of 100% at 100 µg/mL. A field experiment indicated that the difference of efficacy between 5a (75.9%) and dimethomorph (77.1%) at 37.5 g ai/667 m2 was not significant; and 5a also exhibited good activity against Botrytis cinerea by triggering accumulation of PAL and NPR1 defense-related gene expression and the defense associated enzyme phenylalanine ammonia-lyase (PAL) expression on cucumber, rather than direct inhibition. These findings strongly supported that 3,4-dichloroisothiazole containing cinnamamide morpholine 5a not only showed good fungicidal activity against P. cubensis but also exhibited plant innate immunity stimulation activity as a promising fungicide candidate with both fungicidal activity and systemic acquired resistance.


Assuntos
Cinamatos/química , Fungicidas Industriais/síntese química , Tiadiazóis/química , Tiazóis/química , Botrytis/efeitos dos fármacos , Botrytis/crescimento & desenvolvimento , Cinamatos/farmacologia , Cucumis sativus/efeitos dos fármacos , Cucumis sativus/genética , Cucumis sativus/metabolismo , Cucumis sativus/microbiologia , Descoberta de Drogas , Fungicidas Industriais/química , Fungicidas Industriais/farmacologia , Estrutura Molecular , Doenças das Plantas/microbiologia , Relação Estrutura-Atividade , Tiadiazóis/farmacologia
17.
J Agric Food Chem ; 67(41): 11340-11353, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31532201

RESUMO

Inspired by quinine and its analogues, we designed, synthesized, and evaluated two series of quinoline small molecular compounds (a and 2a) and six series of quinoline derivatives (3a-f) for their antifungal activities. The results showed that compounds 3e and 3f series exhibited significant fungicidal activities. Significantly, compounds 3f-4 (EC50 = 0.41 µg/mL) and 3f-28 (EC50 = 0.55 µg/mL) displayed the superior in vitro fungicidal activity and the potent in vivo curative effect against Sclerotinia sclerotiorum. Preliminary mechanism studies showed that compounds 3f-4 and 3f-28 could cause changes in the cell membrane permeability, accumulation of reactive oxygen species, loss of mitochondrial membrane potential, and effective inhibition of germination and formation of S. sclerotiorum sclerotia. These results indicate that compounds 3f-4 and 3f-28 are novel potential fungicidal candidates against S. sclerotiorum derived from natural products.


Assuntos
Fungicidas Industriais/síntese química , Fungicidas Industriais/farmacologia , Quinina/farmacologia , Quinolinas/farmacologia , Ascomicetos/efeitos dos fármacos , Produtos Biológicos/química , Desenho de Fármacos , Fungicidas Industriais/química , Estrutura Molecular , Quinina/química , Quinolinas/química , Relação Estrutura-Atividade
18.
Molecules ; 24(17)2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31470567

RESUMO

BACKGROUND: The development of new antifungal agents has always been a hot research topic in pesticide development. In this study, a series of derivatives of natural compound ß-pinene were prepared, and the antifungal activities of these derivatives were evaluated. The purpose of this work is to develop some novel molecules as promising new fungicides. METHODS: Through a variety of chemical reactions, ß-pinene was transformed into a series of ß-pinene-based derivatives containing amide moieties and acylthiourea moieties. The antifungal activities of these derivatives against five plant pathogens including Colletotrichum gloeosporioides, Fusarium proliferatum, Alternaria kikuchiana, Phomopsis sp. and Phytophthora capsici were tested; preliminary structure-activity relationship was discussed. RESULTS: Some derivatives exhibited moderate or significant antifungal activity due to the fusion of the amide moiety or the acylthiourea moiety with the pinane skeleton. The structure-activity relationship analysis showed that the fluorine atom and the strong electron withdrawing nitro group, or trifluoromethyl group on the benzene ring of the derivatives had a significant effect on the improvement of the antifungal activity against Colletotrichum gloeosporioides, Fusarium proliferatum, Alternaria kikuchiana and Phomopsis sp. Meanwhile, the introduction of an ethyl group at the meta-position on the benzene ring of the derivatives could improve the antifungal activity against Phytophthora capsici. Compounds 4e, 4h, 4q, 4r exhibited broad-spectrum antifungal activity against the tested strains. Compound 4o had significant antifungal activity against Phytophthora capsici (IC50 = 0.18 µmol/L). These derivatives were expected to be used as precursor molecules for novel pesticide development in further research.


Assuntos
Alternaria/efeitos dos fármacos , Monoterpenos Bicíclicos/síntese química , Colletotrichum/efeitos dos fármacos , Fungicidas Industriais/síntese química , Fusarium/efeitos dos fármacos , Phytophthora/efeitos dos fármacos , Sordariales/efeitos dos fármacos , Alternaria/crescimento & desenvolvimento , Amidas/química , Monoterpenos Bicíclicos/farmacologia , Colletotrichum/crescimento & desenvolvimento , Fungicidas Industriais/farmacologia , Fusarium/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Phytophthora/crescimento & desenvolvimento , Doenças das Plantas/microbiologia , Doenças das Plantas/terapia , Plantas/microbiologia , Sordariales/crescimento & desenvolvimento , Relação Estrutura-Atividade , Tioureia/química
19.
J Agric Food Chem ; 67(41): 11354-11363, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31532666

RESUMO

A series of dehydrozingerone derivatives were synthesized, and their fungicidal activities and action mechanism against Colletotrichum musae were evaluated. The bioassay result showed that most compounds exhibited excellent fungicidal activity in vitro at 50 µg mL-1. Compounds 13, 16, 18, 19, and 27 exhibited broad-spectrum fungicidal activity; especially, compounds 19 and 27 were found to have more potent fungicidal activity than azoxystrobin. The EC50 values of compounds 19 and 27 against Rhizoctonia solani were 0.943 and 0.161 µg mL-1 respectively. Moreover, compound 27 exhibited significant in vitro bactericidal activity against Xanthomonas oryzae pv. oryzae, with an EC50 value of 11.386 µg mL-1, and its curative effect (49.64%) and protection effect (51.74%) on rice bacterial blight disease was equivalent to that of zhongshengmycin (42.90%, 40.80% respectively). Compound 27 could also effectively control gray mold (87.10%, 200 µg mL-1) and rice sheath blight (100%, 200 µg mL-1; 82.89%, 100 µg mL-1) in vivo. Preliminary action mechanism study showed that compound 27 mainly acted on the cell membrane and significantly inhibited ergosterol biosynthesis in Colletotrichum musae.


Assuntos
Ergosterol/antagonistas & inibidores , Fungicidas Industriais/síntese química , Fungicidas Industriais/farmacologia , Estirenos/síntese química , Estirenos/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Colletotrichum/efeitos dos fármacos , Colletotrichum/metabolismo , Ergosterol/biossíntese , Fungicidas Industriais/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Oryza/microbiologia , Doenças das Plantas/microbiologia , Rhizoctonia/efeitos dos fármacos , Rhizoctonia/metabolismo , Relação Estrutura-Atividade , Estirenos/química , Xanthomonas/efeitos dos fármacos , Xanthomonas/metabolismo
20.
Bioorg Chem ; 92: 103266, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31542716

RESUMO

In this paper, the nitrogen atom was inserted into the anthracycline system of the isocryptolepine nucleus to obtain the "Aza"-type structure benzo[4,5]imidazo[1,2-c] quinazoline. A series of "Aza"-type derivatives were designed, synthesized and evaluated for their antifungal activity against six plant fungi in vitro. Among all derivatives, compounds A-0, B-1 and B-2 showed significant antifungal activity against B. cinerea with the EC50 values of 2.72 µg/mL, 5.90 µg/mL and 4.00 µg/mL, respectively. Compound A-2 had the highest activity against M. oryzae with the EC50 values of 8.81 µg/mL, and compound A-1 demonstrated the most control efficacy against R. solani (EC50, 6.27 µg/mL). Moreover, compound A-0 was selected to investigate the in vivo tests against B. cinerea and the results indicated that the preventative efficacy of it up to 72.80% at 100 µg/mL. Preliminary mechanism studies revealed that after treatment with A-0 at 5 µg/mL, the B. cinerea mycelia appeared curved, collapsed and the cell membrane integrity may be damaged. The reactive oxygen species production, mitochondrial membrane potential and nuclear morphometry of mycelia have been changed, and the membrane function and cell proliferation of mycelia were destroyed. Compounds A-0, A-1, B-1 and B-2 presented weaker toxicities against two cells lines than isocryptolepine. This study lays the foundation for the future development of isocryptolepine derivatives as environmentally friendly and safe agricultural fungicides.


Assuntos
Antifúngicos/farmacologia , Desenho de Fármacos , Fungos/efeitos dos fármacos , Fungicidas Industriais/farmacologia , Alcaloides Indólicos/farmacologia , Quinolinas/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Relação Dose-Resposta a Droga , Fungicidas Industriais/síntese química , Fungicidas Industriais/química , Alcaloides Indólicos/síntese química , Alcaloides Indólicos/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Plantas/microbiologia , Quinolinas/síntese química , Quinolinas/química , Relação Estrutura-Atividade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...