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1.
J Agric Food Chem ; 68(10): 3071-3078, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32078770

RESUMO

This work reports halogenated 5-(2-hydroxyphenyl)pyrazoles as pseudilin analogues with the potential to target the enzyme IspD in the methylerythritol phosphate (MEP) pathway. Such analogues were designed using the bioisosteric replacement of the pseudilin core structure and synthesized via an efficient three-step route. With AtIspD-based screening and pre- and post-emergence herbicidal tests, these compounds were demonstrated to have considerable activities against AtIspD, with IC50 up to 3.27 µM, and against model plants rape and barnyard grass, with moderate to excellent activities. At a rate of 150 g/ha in the greenhouse test, three compounds exhibited higher or comparable herbicidal activities than pseudilin. Molecular docking of representative compounds into the allosteric site of AtIspD revealed a binding mode similar to that of pseudilin. The established bioisosterism and synthesis method in this work may serve as an important tool for the development of new herbicides and antimicrobials targeting IspD in the MEP pathway.


Assuntos
Echinochloa/enzimologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Herbicidas/química , Herbicidas/farmacologia , Proteínas de Plantas/antagonistas & inibidores , Pirazóis/química , Pirazóis/farmacologia , Echinochloa/efeitos dos fármacos , Echinochloa/genética , Echinochloa/metabolismo , Inibidores Enzimáticos/síntese química , Eritritol/metabolismo , Halogenação , Herbicidas/síntese química , Simulação de Acoplamento Molecular , Estrutura Molecular , Fosfatos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Pirazóis/síntese química , Relação Estrutura-Atividade
2.
J Agric Food Chem ; 67(45): 12538-12546, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31638796

RESUMO

Cyanobacteria harmful algal blooms are of global concern, but all currently available algicides in the market are nonselective and have potential side effects on nontarget species. In the present work, two series of compounds (4 and 6) comprising 16 novel 1,2,3-triazole aminopyrimidines were rationally designed and synthesized as control agent for cyanobacteria. Our design focus was the inhibiting cyanobacteria by inhibition against pyruvate dehydrogenase complex E1 (PDHc-E1). Compounds 4 and 6 showed potent inhibition against Escherichia coli PDHc-E1 (IC50 = 4.13-23.76 µM) and also strong algicidal activities against Synechocystis sp. PCC 6803 (EC50 = 1.7-8.1 µM) and Microcystis sp. FACHB905 (EC50 = 2.1-11.8 µM). In particular, the algicidal activities of 6d against four algal species were not only higher than that of prometryn; they were also comparable to or higher than that of copper sulfate. The analogues 4c, 4d, 6d, and 6e displayed potent algicidal activities and inhibition of E. coli PDHc-E1 but exhibited negligible inhibition of porcine PDHc-E1. As revealed by molecular docking, site-directed mutagenesis, enzymatic assays, and an inhibition kinetic analysis, 4c and 6d inhibited PDHc-E1 in a competitive manner. Our results suggest that highly selective, effective algicides can be developed by rationally designing competitive PDHc-E1 inhibitors.


Assuntos
Proteínas de Bactérias/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Herbicidas/farmacologia , Microcystis/efeitos dos fármacos , Pirimidinas/farmacologia , Piruvato Desidrogenase (Lipoamida)/antagonistas & inibidores , Synechocystis/efeitos dos fármacos , Triazóis/farmacologia , Proteínas de Bactérias/química , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Herbicidas/síntese química , Herbicidas/química , Cinética , Microcystis/química , Microcystis/enzimologia , Simulação de Acoplamento Molecular , Pirimidinas/química , Piruvato Desidrogenase (Lipoamida)/química , Relação Estrutura-Atividade , Synechocystis/química , Synechocystis/enzimologia , Triazóis/química
3.
J Agric Food Chem ; 67(45): 12558-12564, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31609622

RESUMO

All four stereoisomers of naturally occurring 6-(2-hydroxy-6-phenylhex-1-yl)-5,6-dihydro-2H-pyran-2-one (1) were synthesized by employing yeast-reduction products with high optical purity [from 95% enantiomeric excess (ee) to more than 99% ee], and then their phytotoxicities against lettuce and Italian ryegrass were evaluated. In the Italian ryegrass seedlings test, (6S,2'R)-1 showed the most potent and stereospecific activity against the shoots (IC50 = 260 µM) and roots (IC50 = 43.2 µM), with a significant difference from other stereoisomers. The highest seed germination inhibitory activity against Italian ryegrass seed was also observed in (6S,2'R)-1, showing a 53% germination ratio from the control at 1000 µM. This advantageous (6S,2'R) stereochemistry was employed in the syntheses of α,ß-dihydro, 2'-dehydroxy, and 2'-methoxy derivatives 13-15. By the test using these derivatives, the importance of the α,ß-unsaturated double bond and hydroxy group bonding to a chiral center on the 6-alkyl chain of 5,6-dihydro-α-pyrone for phytotoxicity was determined. In the test against lettuce, the 6S configuration and (6S,2'S) configuration were necessary for growth inhibition (IC50 = ca. 60 µM) and germination inhibition (63% germination ratio at 1000 µM), respectively.


Assuntos
Carbono/química , Herbicidas/farmacologia , Piranos/química , Carbono/farmacologia , Germinação/efeitos dos fármacos , Herbicidas/síntese química , Herbicidas/química , Alface/efeitos dos fármacos , Alface/crescimento & desenvolvimento , Lolium/efeitos dos fármacos , Lolium/crescimento & desenvolvimento , Estrutura Molecular , Piranos/farmacologia , Estereoisomerismo , Relação Estrutura-Atividade
4.
J Agric Food Chem ; 67(43): 11839-11847, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31589436

RESUMO

4-Hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) is an important target site for discovering new bleaching herbicides. To explore novel HPPD inhibitors with excellent herbicidal activity, a series of novel N-aroyl diketone/triketone derivatives were rationally designed by splicing active groups and bioisosterism. Bioassays revealed that most of these derivatives displayed preferable herbicidal activity against Echinochloa crus-galli (EC) at 0.045 mmol/m2 and Abutilon juncea (AJ) at 0.090 mmol/m2. In particular, compound I-f was more potent compared to the commercialized compound mesotrione. Molecular docking indicated that the corresponding active molecules of target compounds and mesotrione shared similar interplay with surrounding residues, which led to a perfect interaction with the active site of Arabidopsis thaliana HPPD.


Assuntos
4-Hidroxifenilpiruvato Dioxigenase/antagonistas & inibidores , Inibidores Enzimáticos/química , Herbicidas/química , Cetonas/química , Proteínas de Plantas/antagonistas & inibidores , 4-Hidroxifenilpiruvato Dioxigenase/química , 4-Hidroxifenilpiruvato Dioxigenase/metabolismo , Domínio Catalítico , Echinochloa/efeitos dos fármacos , Echinochloa/enzimologia , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Herbicidas/síntese química , Herbicidas/farmacologia , Cetonas/farmacologia , Malvaceae/efeitos dos fármacos , Malvaceae/enzimologia , Simulação de Acoplamento Molecular , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Plantas Daninhas/efeitos dos fármacos , Plantas Daninhas/enzimologia , Relação Estrutura-Atividade
5.
J Agric Food Chem ; 67(39): 10844-10852, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31525997

RESUMO

The discovery of 4-hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) inhibitors has been an active area of research due to their great potential as herbicides for weed control. Starting from the binding mode of known inhibitors of HPPD, a series of HPPD inhibitors with new molecular scaffolds were designed and synthesized by hybridizing 2-benzoylethen-1-ol and isoindoline-1,3-dione fragments. The results of the in vitro tests indicated that the newly synthesized compounds showed good HPPD inhibitory activity with IC50 values against the recombinant Arabidopsis thaliana HPPD (AtHPPD) ranging from 0.0039 µM to over 1 µM. Most promisingly, compound 4ae, 2-benzyl-5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4- carbonyl)isoindoline-1,3-dione, showed the highest AtHPPD inhibitory activity with a Ki value of 3.92 nM, making it approximately 10 times more potent than pyrasulfotole (Ki = 44 nM) and slightly more potent than mesotrione (Ki = 4.56 nM). In addition, the cocrystal structure of the AtHPPD-4ae complex was successfully resolved at a resolution of 1.8 Å. The X-ray diffraction analysis indicated that the two carbonyl groups of 2-benzoylethen-1-ol formed a bidentate chelating interaction with the metal ion, while the isoindoline-1,3-dione moiety formed pronounced π-π stacking interactions with Phe381 and Phe424. Moreover, water-mediated hydrogen bonding interactions were observed between Asn282 and the nitrogen atoms of the pyrazole ring of 4ae. The above results showed that the pyrazole-isoindoline-1,3-dione hybrid is a promising scaffold for developing HPPD inhibitors.


Assuntos
4-Hidroxifenilpiruvato Dioxigenase/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Herbicidas/farmacologia , Isoindóis/farmacologia , Proteínas de Plantas/antagonistas & inibidores , Pirazóis/farmacologia , 4-Hidroxifenilpiruvato Dioxigenase/química , 4-Hidroxifenilpiruvato Dioxigenase/metabolismo , Arabidopsis/efeitos dos fármacos , Arabidopsis/crescimento & desenvolvimento , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Herbicidas/síntese química , Herbicidas/química , Isoindóis/química , Cinética , Estrutura Molecular , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Plantas Daninhas/efeitos dos fármacos , Plantas Daninhas/crescimento & desenvolvimento , Pirazóis/química , Relação Estrutura-Atividade
6.
Molecules ; 24(17)2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31484319

RESUMO

A novel synthetic strategy for obtainment of (±)-3-deoxyradicinin (2) is reported. This synthetic methodology is more efficient than those previously reported in the literature and also shows higher versatility towards the introduction of different side-chains at both C-7 and C-2. The obtained compound (±)-2 shows phytotoxicity against the grass-weed buffelgrass comparable to that of the natural phytotoxin radicinin (1). Therefore, (±)-2 can constitute a more practical synthetic alternative to 1 as bioherbicide for buffelgrass control.


Assuntos
Cenchrus/efeitos dos fármacos , Herbicidas/síntese química , Herbicidas/farmacologia , Pironas/metabolismo , Herbicidas/química
7.
J Agric Food Chem ; 67(37): 10489-10497, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31452371

RESUMO

In order to develop a novel herbicide containing the ß-triketone motif, a series of 4-hydroxyl-3-(2-phenoxyacetyl)-pyran-2-one derivatives were designed and synthesized. The bioassay results showed that compound II15 had good pre-emergent herbicidal activity even at a dosage of 187.5 g ha-1. Moreover, compound II15 showed a broader spectrum of weed control when compared with a commercial herbicide 2,4-dichlorophenoxyacetic acid (2,4-D), and displayed good crop safety to Triticum aestivum L. and Zea mays Linn. when applied at 375 g ha-1 under pre-emergence conditions, which indicated its great potential as a herbicide. More importantly, studying the molecular mode of action of compound II15 revealed that the novel triketone structure is a proherbicide of its corresponding phenoxyacetic acid auxin herbicide, which has a herbicidal mechanism similar to that of 2,4-D. The present work indicates that the 4-hydroxyl-3-(2-phenoxyacetyl)-pyran-2-one motif may be a potential lead structure for further development of novel auxin-type herbicides.


Assuntos
Herbicidas/síntese química , Herbicidas/farmacologia , Plantas Daninhas/efeitos dos fármacos , Arabidopsis/efeitos dos fármacos , Desenho de Drogas , Herbicidas/química , Estrutura Molecular , Plantas Daninhas/crescimento & desenvolvimento , Relação Estrutura-Atividade , Controle de Plantas Daninhas , Zea mays/efeitos dos fármacos
8.
J Agric Food Chem ; 67(28): 7783-7792, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31267752

RESUMO

The increasing use of pesticides in agriculture and gardening has caused severe deterioration to both the ecosystem and the health of users (human beings), so there is an urgent need for eco- and user-friendly pesticides. Among a variety of herbicides, paraquat (PQ), frequently used as an effective herbicidal agent worldwide, is well-known for its serious toxicity that has killed, and harmed, thousands of people and countless wildlife such as fish. Herein, we present a facile supramolecular formulation of PQ@cucurbit[7]uril (PQ@CB[7]), prepared by simply mixing PQ with equivalent (molar) CB[7] in water. With addition of CB[7], PQ's cellular uptake was dramatically inhibited. The reactive oxygen species (ROS) generation and the associated apoptosis otherwise induced by PQ in cellular models were both reduced, resulting in increased cellular viability. In a wildtype zebrafish model that is a typical fragile wildlife species in the ecosystem, the supramolecular formulation exhibited significantly reduced hepatotoxicity and increased survival rate, in comparison with those of the fish exposed to free PQ. In a mouse model that is clinically relevant to human being, the administration of PQ@CB[7] significantly alleviated major organ injuries and unusual hematological parameters that were otherwise induced by free PQ, resulting in a significantly increased survival rate. Meanwhile, this formulation maintained effective herbicidal activity that was equivalent to that of free PQ. Taken together, this facile supramolecular PQ formulation is providing not only an extremely rare example of an eco- and user-friendly herbicide that has been desired for decades but also a practical solution for green agriculture.


Assuntos
Herbicidas/farmacologia , Paraquat/farmacologia , Animais , Apoptose/efeitos dos fármacos , Química Verde , Herbicidas/síntese química , Herbicidas/química , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacos , Paraquat/síntese química , Paraquat/química , Poaceae/efeitos dos fármacos , Poaceae/crescimento & desenvolvimento , Peixe-Zebra/metabolismo
9.
Molecules ; 24(14)2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31336669

RESUMO

A new and direct approach to the construction of the core framework of the herbicidal natural products cornexistin and hydroxycornexistin has been developed. Formation of the nine-membered carbocycle found in the natural products has been accomplished by an intramolecular Nozaki-Hiyama-Kishi reaction between a vinylic iodide and an aldehyde. Good yields of carbocyclic products were obtained from the reaction, but diastereomeric mixtures of allylic alcohols were produced. The cyclisation reaction was successful irrespective of the relative configuration of the stereogenic centres in the cyclisation precursor.


Assuntos
Técnicas de Química Sintética , Furanos/síntese química , Produtos Biológicos/síntese química , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Furanos/química , Furanos/farmacologia , Herbicidas/síntese química , Herbicidas/química , Estrutura Molecular , Acoplamento Oxidativo
10.
Chemistry ; 25(44): 10333-10341, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31187904

RESUMO

(5S,6S)-Aminotenuazonic acid, a new 3-acyltetramic acid, related to the well-known mycotoxin tenuazonic acid has been isolated from fruiting bodies of Laccaria bicolor. Its structure was mostly established by analysis of its 2D NMR and HR-(+)-ESI-MS spectra. A total synthesis starting from N-Boc-l-isoleucine gave (5S,6S)-aminotenuazonic acid in 8 % yield over nine steps (67 % de). The key steps of the total synthesis are a light-initiated Hofmann-Löffler-Freytag radical chain reaction and a Dieckmann cyclisation. The relative and absolute configurations of the natural product were determined by comparison of its NMR and CD spectra with those of the corresponding enantiopure synthetic compounds. Metabolic profiling of crude extracts of different mushrooms showed that aminotenuazonic acid is present in all four of the investigated Laccaria species. Aminotenuazonic acid shows phytotoxic activities against the root and shoot growth of Lepidium sativum, Pinus sylvestris and Arabidopsis thaliana comparable to those of tenuazonic acid.


Assuntos
Carpóforos/química , Herbicidas/isolamento & purificação , Laccaria/química , Ácido Tenuazônico/análogos & derivados , Ácido Tenuazônico/isolamento & purificação , Arabidopsis , Catálise , Ciclização , Herbicidas/síntese química , Lepidium sativum , Oxirredução , Pinus sylvestris , Raízes de Plantas , Brotos de Planta , Ácido Tenuazônico/síntese química
11.
Top Curr Chem (Cham) ; 377(3): 14, 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31062103

RESUMO

Quaternary ammonium compounds, referred to as QACs, are cationic substances with a structure on the edge of organic and inorganic chemistry and unique physicochemical properties. The purpose of the present work is to introduce QACs and their wide application potential. Fundamental properties, methods of preparation, and utilization in organic synthesis are reviewed. Modern applications and the use of QACs as reactive substrates, reagents, phase-transfer catalysts, ionic liquids, electrolytes, frameworks, surfactants, herbicides, and antimicrobials are further covered. A brief discussion of the health and environmental impact of QACs is also provided. The emphasis is largely on tetraalkylammonium compounds bearing linear alkyl chains.


Assuntos
Anti-Infecciosos/química , Herbicidas/química , Compostos de Amônio Quaternário/química , Tensoativos/química , Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Herbicidas/síntese química , Herbicidas/farmacologia , Compostos de Amônio Quaternário/síntese química , Compostos de Amônio Quaternário/farmacologia , Tensoativos/síntese química , Tensoativos/farmacologia
12.
Photochem Photobiol Sci ; 18(6): 1350-1358, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-30915429

RESUMO

Indole derivatives were synthetized based on the Fischer indole methodology using different phenyl hydrazine hydrochlorides and either cyclohexanone or 2-butanone. The pre- and post-emergent herbicidal activities were evaluated against Ipomoea grandifolia. A carbazole, 6-chloro-2,3,4,9-tetrahydro-1H-carbazole (3b), decreased the PIabs parameter by 32% and increased the cross-section related parameters, indicating the inactivation of the reaction center on photosystem II. Compound 3b acts as a post-emergent herbicide prototype since dry biomass was reduced by 50%, corroborating the fluorescence results. Comparing instead with a germination experiment, 2,3,4,9-tetrahydro-1H-carbazole (3a) was found to be the most effective agent, inhibiting seed germination by 22% and decreasing root length by 50%. The tetrahydrocarbazoles showed better results than indole derivatives potentially due to the presence of methylene groups at structures, which increase the compounds' lipophilicity and may facilitate their access to the plant. In addition, electron withdrawing groups on the aromatic ring were found to correlate with increased herbicide activity. Further optimization of this series towards the development of herbicides is ongoing.


Assuntos
Inibidores do Crescimento/farmacologia , Herbicidas/farmacologia , Indóis/farmacologia , Ipomoea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Inibidores do Crescimento/síntese química , Inibidores do Crescimento/química , Herbicidas/síntese química , Herbicidas/química , Indóis/síntese química , Indóis/química , Ipomoea/crescimento & desenvolvimento , Estrutura Molecular , Relação Estrutura-Atividade
13.
Eur J Med Chem ; 167: 472-484, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30784880

RESUMO

Since pyrithiobac (PTB) is a successful commercial herbicide with very low toxicity against mammals, it is worth exploring its derivatives for an extensive study. Herein, a total of 35 novel compounds were chemically synthesized and single crystal of 6-6 was obtained to confirm the molecular structure of this family of compounds. The novel PTB derivatives were fully evaluated against various biological platforms. From the bioassay results, the best AHAS inhibitor 6-22 displayed weaker herbicidal activity but stronger anti-Candida activity than PTB did. For plant pathogenic fungi, 6-26 showed excellent activity at 50 mg/L dosage. Preliminary insecticidal activity and antiviral activity were also observed for some title compounds. Strikingly, 6-5 exhibited a promising inhibitory activity against SARS-CoV Mpro with IC50 of 4.471 µM and a low cellular cytotoxicity against mammalian 293 T cells. Based on the results of molecular modeling, HOMO-1 was considered to be a factor that affects AHAS inhibition and a possible binding mode of 6-5 with SARS-CoV Mpro was predicted. This is the first time that PTB derivatives have been studied as biological agents other than herbicides. The present research hence has suggested that more attentions should be paid to compounds belonging to this family to develop novel agrochemicals or medicines.


Assuntos
Benzoatos/síntese química , Benzoatos/farmacologia , Fungos/efeitos dos fármacos , Herbicidas/síntese química , Acetolactato Sintase/antagonistas & inibidores , Antivirais/síntese química , Antivirais/farmacologia , Benzoatos/química , Desenho de Drogas , Herbicidas/farmacologia , Herbicidas/uso terapêutico , Modelos Moleculares , Estrutura Molecular , Vírus da SARS/efeitos dos fármacos
14.
Bioorg Med Chem ; 27(5): 805-812, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30711311

RESUMO

By using a new Fragment-Based Virtual Screen strategy, two series of novel FBA-II inhibitors (thiourea derivatives) were de novo discovered based on the active site of fructose-1, 6-bisphosphate aldolase from Cyanobacterial (CyFBA). In comparison, most of the N-(2-benzoylhydrazine-1-carbonothioyl) benzamide derivatives (L14∼L22) exhibit higher CyFBA-II inhibitory activities compared to N-(phenylcarbamothioyl) benzamide derivatives (L1∼L13). Especially, compound L14 not only shows higher CyFBA-II activity (Ki = 0.65 µM), but also exhibits most potent in vivo activity against Synechocystis sp. PCC 6803 (EC50 = 0.09 ppm), higher (7-fold) than that of our previous inhibitor (EC50 = 0.6 ppm). The binding modes of compound L14 and CyFBA-II were further elucidated by jointly using DOX computational protocol, MM-PBSA and site-directed mutagenesis assays. The positive results suggest that strategy adopted in this study was promising to rapidly discovery the potent inhibitors with novel scaffolds. The satisfactory algicide activities suggest that the thiourea derivatives is very likely to be a promising lead for the development of novel specific algicides to solve Cyanobacterial harmful algal blooms (CHABs).


Assuntos
Antibacterianos/farmacologia , Inibidores Enzimáticos/farmacologia , Frutose-Bifosfato Aldolase/antagonistas & inibidores , Herbicidas/farmacologia , Tioureia/análogos & derivados , Tioureia/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Desenho de Drogas , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Frutose-Bifosfato Aldolase/química , Frutose-Bifosfato Aldolase/genética , Herbicidas/síntese química , Herbicidas/química , Simulação de Dinâmica Molecular , Mutagênese Sítio-Dirigida , Mutação , Synechocystis/efeitos dos fármacos , Synechocystis/enzimologia , Tioureia/síntese química
15.
Pest Manag Sci ; 75(7): 2049-2056, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30632264

RESUMO

BACKGROUND: Strigolactones are a unique class of plant metabolites which serve as a rhizosphere signal for parasitic plants and evocate their seed germination. The expansion of these parasitic weeds in the food crop fields urgently calls for their increased control and depletion. Simple strigolactone analogues able to stimulate seed germination of these parasitic plants may represent an efficient control measure through the induction of suicidal germination. RESULTS: Triazolide-type strigolactone mimics were easily synthesized in three steps from commercially available materials. These derivatives induced effectively seed germination of Phelipanche ramosa with EC50 as low as 5.2 × 10-10 M. These mimics did not induce seed germination of Striga hermonthica even at high concentration (≥1 × 10-5 M). CONCLUSIONS: Simple and stable strigolactone mimics with selective activity against Phelipanche ramosa were synthesized. © 2019 Society of Chemical Industry.


Assuntos
Germinação/efeitos dos fármacos , Lactonas/síntese química , Lactonas/farmacologia , Orobanchaceae/efeitos dos fármacos , Herbicidas/síntese química , Herbicidas/farmacologia , Plantas Daninhas/efeitos dos fármacos , Sementes/efeitos dos fármacos
16.
Nat Prod Res ; 33(17): 2453-2460, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29569471

RESUMO

Taking natural product phenazine-1-carboxamide (PCN) as a lead compound, a series of novel phenazine-1-carboxylic acid diamide derivatives were designed and synthesised. Their structures were confirmed by 1H-NMR and HRMS. The bioassays showed that some of the target compounds exhibited promising in vitro fungicidal activities, and exhibited excellent and selective herbicidal activities. Particularly, compounds c, h, o and s displayed root length inhibition activities against barnyard grass with the rate of more than 80%. Compound c exhibited the best activity among all the target compounds against barnyard grass stalk length with the IC50 value of 0.158 mmol/L, and compound o exhibited the best and wide spectrum inhibition against barnyard grass root length and rape in both root length and stalk length herbicidal activities with its IC50 values of 0.067, 0.048 and 0.059 mmol/L respectively. The analysis of preliminary Structure-Activity Relationships provides the theoretical basis for further design of phenazine-1-carboxylic acid.


Assuntos
Diamida/química , Fungicidas Industriais/farmacologia , Herbicidas/síntese química , Herbicidas/farmacologia , Fenazinas/química , Echinochloa/efeitos dos fármacos , Fungicidas Industriais/síntese química , Herbicidas/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Relação Estrutura-Atividade
17.
Molecules ; 23(12)2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30513789

RESUMO

Background: The aim of this work was to evaluate phytotoxicity of the thiophene derivatives against three persistent weeds of a high degree of resistance (Galinsoga parviflora Cav., Rumex acetosa L., and Chenopodium album) as well as their ecotoxicological impact on Heterocypris incongruens. In addition, Aliivibrio fischeri was measured. Two of eight described aminophosphonates, namely dimethyl N-(2-methoxyphenyl)amino(2-thienyl)methylphosphonate (2d) and dimethyl N-(tert-butyl)- (2-thienyl)methylphosphonate (2h), have never been reported before. Methods: The phytotoxicity of tested aminophosphonates toward their potential application as soil-applied herbicides was evaluated according to the OECD 208 Guideline. Ecotoxicological properties of investigated compounds were made using the OSTRACODTOXKITTM and Microtox® tests. Results: Obtained results showed that four aminophosphonates have interesting herbicidal properties and N-(2-methylphenyl)amino- (2-thienyl)methylphosphonate (2a) was found to kill efficiently the most resistant plant Chenopodium album. None of the tested compounds showed important toxicity against Aliivibrio fischeri. However, their toxic impact on Heterocypris incongruens was significantly elevated. Conclusions: The aminophosphonate 2a showed herbicidal potential and it is not toxic against tested bacteria (EC50 over 1000 mg/L). It was found to be moderately toxic against ostracods [mortality 48% at 10 mg/kg of soil dry weight (s.d.w.)] and this problem should be solved by the use of the controlled release from a polymeric carrier.


Assuntos
Agricultura , Herbicidas/química , Herbicidas/farmacologia , Plantas Daninhas/efeitos dos fármacos , Plantas Daninhas/crescimento & desenvolvimento , Tiofenos/química , Tiofenos/farmacologia , Relação Dose-Resposta a Droga , Herbicidas/síntese química , Fenótipo , Tiofenos/síntese química
18.
ACS Chem Biol ; 13(9): 2585-2594, 2018 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-30138566

RESUMO

Indole-3-acetic acid (auxin) is considered one of the cardinal hormones in plant growth and development. It regulates a wide range of processes throughout the plant. Synthetic auxins exploit the auxin-signaling pathway and are valuable as herbicidal agrochemicals. Currently, despite a diversity of chemical scaffolds all synthetic auxins have a carboxylic acid as the active core group. By applying bio-isosteric replacement we discovered that indole-3-tetrazole was active by surface plasmon resonance spectrometry, showing that the tetrazole could initiate assembly of the Transport Inhibitor Resistant 1 (TIR1) auxin coreceptor complex. We then tested the tetrazole's efficacy in a range of whole plant physiological assays and in protoplast reporter assays, which all confirmed auxin activity, albeit rather weak. We then tested indole-3-tetrazole against the AFB5 homologue of TIR1, finding that binding was selective against TIR1, absent with AFB5. The kinetics of binding to TIR1 are contrasted to those for the herbicide picloram, which shows the opposite receptor preference, as it binds to AFB5 with far greater affinity than to TIR1. The basis of the preference of indole-3-tetrazole for TIR1 was revealed to be a single residue substitution using molecular docking, and assays using tir1 and afb5 mutant lines confirmed selectivity in vivo. Given the potential that a TIR1-selective auxin might have for unmasking receptor-specific actions, we followed a rational design, lead optimization campaign, and a set of chlorinated indole-3-tetrazoles was synthesized. Improved affinity for TIR1 and the preference for binding to TIR1 was maintained for 4- and 6-chloroindole-3-tetrazoles, coupled with improved efficacy in vivo. This work expands the range of auxin chemistry for the design of receptor-selective synthetic auxins.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Proteínas F-Box/metabolismo , Herbicidas/metabolismo , Ácidos Indolacéticos/metabolismo , Reguladores de Crescimento de Planta/metabolismo , Receptores de Superfície Celular/metabolismo , Tetrazóis/metabolismo , Arabidopsis/crescimento & desenvolvimento , Halogenação , Herbicidas/síntese química , Herbicidas/química , Ácidos Indolacéticos/síntese química , Ácidos Indolacéticos/química , Simulação de Acoplamento Molecular , Reguladores de Crescimento de Planta/síntese química , Reguladores de Crescimento de Planta/química , Ligação Proteica , Tetrazóis/síntese química , Tetrazóis/química
19.
Sci Rep ; 8(1): 8555, 2018 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-29867206

RESUMO

Currently, harmful algal blooms are being one of ever-increasing global environmental problems. Much attention has been paid to the use of natural products as the selective algaecides due to their low toxicity, high selectivity and eco-friendly properties. In the present study, the thiazole alkaloid (1), originally isolated from Thermoactino-myces strain TM-64, was shown to exhibit potent algicidal activity against three typically harmful cyanobacterial algae, S. obliqnus, M. aeruginosa, and C. pyrenoidosa. Based on our previous work, a practical, scalable synthesis of alkaloid (1) was developed and reaction could be readily scaled up to more than 100 g. In addition, twenty-six analogues of alkaloid (1) by replacement of tryptamine moiety with different aromatic and aliphatic amines were also prepared. The bioassay results showed that most of these derivatives displayed potent algicidal activity against three harmful algae S. obliqnus, M. aeruginosa, and C. pyrenoidosa with IC50 values in the range of 1.5-5.0 µg/mL. Amongst them, compounds (10) and its hydrochloric salt (10S) were found to reveal powerful growth inhibitory activity against harmful cyanobacterial algae with IC50 values as low as 0.08 µg/mL, comparable to those of commercial algicide CuSO4 and herbicide Diuron.


Assuntos
Amidas , Cianobactérias/crescimento & desenvolvimento , Herbicidas , Tiazóis , Amidas/síntese química , Amidas/química , Amidas/farmacologia , Herbicidas/síntese química , Herbicidas/química , Herbicidas/farmacologia , Tiazóis/síntese química , Tiazóis/química , Tiazóis/farmacologia
20.
Molecules ; 23(6)2018 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-29925805

RESUMO

This review summarizes the main synthetic routes towards α-hydroxyphosphonates that are known as enzyme inhibitors, herbicides and antioxidants, moreover, a number of representatives express antibacterial or antifungal effect. Special attention is devoted to green chemical aspects. α-Hydroxyphosphonates are also versatile intermediates for other valuable derivatives. O-Alkylation and O-acylation are typical reactions to afford α-alkoxy-, or α-acyloxyphosphonates, respectively. The oxidation of hydroxyphosphonates leads to ketophosphonates. The hydroxy function at the α carbon atom of hydroxyphosphonates may be replaced by a halogen atom. α-Aminophosphonates formed in the nucleophilic substitution reaction of α-hydroxyphosphonates with primary or secondary amines are also potentially bioactive compounds. Another typical reaction is the base-catalyzed rearrangement of α-hydroxy-phosphonates to phosphates. Hydrolysis of the ester function of hydroxyphosphonates leads to the corresponding phosphonic acids.


Assuntos
Organofosfonatos/síntese química , Animais , Antioxidantes/síntese química , Antioxidantes/química , Catálise , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Herbicidas/síntese química , Herbicidas/química , Humanos , Estrutura Molecular , Organofosfonatos/química , Oxirredução , Estereoisomerismo , Relação Estrutura-Atividade
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