RESUMEN

Effective microorganisms (EM) might alleviate deterioration of soil environmental quality and yield decline of pepper (Capsicum annuum) caused by continuous replanting and imbalanced fertilizer application in Xinjiang. We investigated the effects of applying EM microbial agent on the growth of pepper plants, yield, soil nutrient content, soil enzyme activity, and rhizosphere eukaryotic community. The results showed that the application of EM microbial agent increased plant height, stem diameter, leaf length, leaf width and root length by 22.6%, 35.3%, 33.3%, 29.7% and 15.1%, respectively. It also increased fruit width, individual fruit weight, and yield by 5.3%, 42.9%, and 74.7%, respectively. After the application of EM microbial agent, the levels of soil available nitrogen increased by 10.2% and 5.8% during the flowering and maturity stages, respectively. Similarly, available phosphorus increased by 10.4% and 13.4%, respectively. The soil sucrase activity was increased by 40.7%, 14.6%, and 9.3% during the seedling, flowering, and maturity stages, respectively. Urease activity was also increased by 7.9%, 10.2%, and 11.5%, respectively. Furthermore, the application of EM microbial agent increased soil peroxidase activity by 16.8% and 44.6% at flowering and maturity stages, respectively. The application of microbial agent significantly altered the ß-diversity of the rhizosphere eukaryotic community in pepper plants. Specifically, microbial agent increased the relative abundances of populations belonging to Enchytraeus and Sminthurides genera, which could contribute to soil improvement and nutrient cycling. Compared to the CK, the relative abundance of pathogenic microorganisms including Olpidium and Aplanochytrium genera decreased by 98.0% and 89.3%, and the relative abundance of the Verticillium decreased to 0. These results demonstrated that EM microbial agent could increase soil nutrient content, enhance soil enzyme activity, and reduce soil pathogenic fungi in the pepper cultivation areas of Xinjiang, thus achieving beneficial effects on pepper growth and fruit yield.

Asunto(s)

Capsicum , Rizosfera , Microbiología del Suelo , Capsicum/crecimiento & desarrollo , Capsicum/microbiología , China , Suelo/química , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/microbiología , Raíces de Plantas/metabolismo

RESUMEN

Abscisic acid (ABA) is the primary preventing factor of seed germination, which is crucial to plant survival and propagation. ABA-induced seed germination inhibition is mainly mediated by the dimeric PYR/PYL/RCAR (PYLs) family members. However, little is known about the relevance between dimeric stability of PYLs and seed germination. Here, we reveal that stabilization of PYL dimer can relieve ABA-induced inhibition of seed germination using chemical genetic approaches. Di-nitrobensulfamide (DBSA), a computationally designed chemical probe, yields around ten-fold improvement in receptor affinity relative to ABA. DBSA reverses ABA-induced inhibition of seed germination mainly through dimeric receptors and recovers the expression of ABA-responsive genes. DBSA maintains PYR1 in dimeric state during protein oligomeric state experiment. X-ray crystallography shows that DBSA targets a pocket in PYL dimer interface and may stabilize PYL dimer by forming hydrogen networks. Our results illustrate the potential of PYL dimer stabilization in preventing ABA-induced seed germination inhibition.

Asunto(s)

Ácido Abscísico , Proteínas de Arabidopsis , Arabidopsis , Germinación , Semillas , Germinación/efectos de los fármacos , Ácido Abscísico/metabolismo , Ácido Abscísico/farmacología , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Arabidopsis/crecimiento & desarrollo , Arabidopsis/efectos de los fármacos , Arabidopsis/metabolismo , Arabidopsis/genética , Semillas/efectos de los fármacos , Semillas/crecimiento & desarrollo , Semillas/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Multimerización de Proteína/efectos de los fármacos , Cristalografía por Rayos X , Sulfonamidas/farmacología , Sulfonamidas/química , Proteínas de Transporte de Membrana

RESUMEN

The woody bamboos (Bambusoideae) exhibit distinctive biological traits within Poaceae, such as highly lignified culms, rapid shoot growth, monocarpic mass flowering and nutlike or fleshy caryopses. Much of the remarkable morphological diversity across the subfamily exists within a single hexaploid clade, the paleotropical woody bamboos (PWB), making it ideal to investigate the factors underlying morphological evolution in woody bamboos. However, the origin and biogeographical history of PWB remain elusive, as does the effect of environmental factors on the evolution of their morphological characters. We generated a robust and time-calibrated phylogeny of PWB using single nucleotide polymorphisms retrieved from optimized double digest restriction site associated DNA sequencing, and explored the evolutionary trends of habit, inflorescence, and caryopsis type in relation to environmental factors including climate, soil, and topography. We inferred that the PWB started to diversify across the Oligocene-Miocene boundary and formed four major clades, that is, Melocanninae, Racemobambosinae s.l. (comprising Dinochloinae, Greslanlinae, Racemobambosinae s.str. and Temburongiinae), Hickeliinae and Bambusinae s.l. (comprising Bambusinae s.str. plus Holttumochloinae). The ancestor of PWB was reconstructed as having erect habit, indeterminate inflorescence and basic caryopsis. The characters including climbing/scrambling habit, determinate inflorescence, and nucoid/bacoid caryopsis have since undergone multiple changes and reversals during the diversification of PWB. The evolution of all three traits was correlated with, and hence likely influenced by, aspects of climate, topography, and soil, with climate factors most strongly correlated with morphological traits, and soil factors least so. However, topography had more influence than climate or soil on the evolution of erect habit, whereas both factors had greater effect on the evolution of bacoid caryopsis than did soil. Our results provide novel insights into morphological diversity and adaptive evolution in bamboos for future ecological and evolutionary research.

RESUMEN

5-(3'-Indolyl)oxazole moiety is a privileged heterocyclic scaffold, embedded in many biologically interesting natural products and potential therapeutic agents. Compounds containing this scaffold, whether from natural sources or synthesized, have demonstrated a wide array of biological activities. This has piqued the interest of synthetic chemists, leading to a large number of reported synthetic approaches to 5-(3'-indolyl)oxazole scaffold in recent years. In this review, we comprehensively overviewed the different biological activities and chemical synthetic methods for the 5-(3'-indolyl)oxazole scaffold reported in the literatures from 1963 to 2024. The focus of this study is to highlight the significance of 5-(3'-indolyl)oxazole derivatives as the lead compounds for the lead discovery of anticancer, pesticidal, antimicrobial, antiviral, antioxidant and anti-inflammatory agents, to summarize the synthetic methods for the 5-(3'-indolyl)oxazole scaffold. In addition, the reported mechanism of action of 5-(3'-indolyl)oxazoles and advanced molecules studied in animal models are also reviewed. Furthermore, this review offers perspectives on how 5-(3'-indolyl)oxazole scaffold as a privileged structure might be exploited in the future.

RESUMEN

Cadmium (Cd) has become an important heavy metal pollutant because of its strong migration and high toxicity. The industrial production process aggravated the Cd pollution in rice fields. Human exposure to Cd through rice can cause kidney damage, emphysema, and various cardiovascular and metabolic diseases, posing a grave threat to health. As modern technology develops, the Cd accumulation model in rice and in-situ remediation of Cd pollution in cornfields have been extensively studied and applied, so it is necessary to sort out and summarize them systematically. Therefore, this paper reviewed the primary in-situ methods for addressing heavy metal contamination in rice paddies, including chemical remediation (inorganic-organic fertilizer remediation, nanomaterials, and composite remediation), biological remediation (phytoremediation and microbial remediation), and crop management remediation technologies. The factors that affect Cd transformation in soil and Cd migration in crops, the advantages and disadvantages of remediation techniques, remediation mechanisms, and the long-term stability of remediation were discussed. The shortcomings and future research directions of in situ remediation strategies for heavily polluted paddy fields and genetic improvement strategies for low-cadmium rice varieties were critically proposed. To sum up, this review aims to enhance understanding and serve as a reference for the appropriate selection and advancement of remediation technologies for rice fields contaminated with heavy metals.

Asunto(s)

Biodegradación Ambiental , Cadmio , Restauración y Remediación Ambiental , Oryza , Rizosfera , Contaminantes del Suelo , Restauración y Remediación Ambiental/métodos , Fertilizantes , Humanos , Agricultura/métodos , Semillas/química

RESUMEN

Discovering and engineering herbicide-resistant genes is a crucial challenge in crop breeding. This study focuses on the 4-hydroxyphenylpyruvate dioxygenase Inhibitor Sensitive 1-Like (HSL) protein, prevalent in higher plants and exhibiting weak catalytic activity against many ß-triketone herbicides (ß-THs). The crystal structures of maize HSL1A complexed with ß-THs were elucidated, identifying four essential herbicide-binding residues and explaining the weak activity of HSL1A against the herbicides. Utilizing an artificial evolution approach, we developed a series of rice HSL1 mutants targeting the four residues. Then, these mutants were systematically evaluated, identifying the M10 variant as the most effective in modifying ß-THs. The initial active conformation of substrate binding in HSL1 was also revealed from these mutants. Furthermore, overexpression of M10 in rice significantly enhanced resistance to ß-THs, resulting in a notable 32-fold increase in resistance to methyl-benquitrione. In conclusion, the artificially evolved M10 gene shows great potential for the development of herbicide-resistant crops.

Asunto(s)

Resistencia a los Herbicidas , Herbicidas , Oryza , Proteínas de Plantas , Oryza/genética , Oryza/metabolismo , Resistencia a los Herbicidas/genética , Herbicidas/farmacología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fitomejoramiento/métodos , Plantas Modificadas Genéticamente/genética , Mutación

RESUMEN

Mycorrhizal associations are key mutualisms that shape the structure of forest communities and multiple ecosystem functions. However, we lack a framework for predicting the varying dominance of distinct mycorrhizal associations in an integrated proxy of multifunctionality across ecosystems. Here, we used the datasets containing diversity of mycorrhizal associations and 18 ecosystem processes related to supporting, provisioning, and regulating services to examine how the dominance of ectomycorrhiza (EcM) associations affects ecosystem multifunctionality in subtropical mountain forests in Southwest China. Meanwhile, we synthesized the prevalence of EcM-dominant effects on ecosystem functioning in forest biomes. Our results demonstrated that elevation significantly modified the distributions of EcM trees and fungal dominance, which in turn influenced multiple functions simultaneously. Multifunctionality increased with increasing proportion of EcM associations, supporting the ectomycorrhizal-dominance hypothesis. Meanwhile, we observed that the impacts of EcM dominance on individual ecosystem functions exhibited different relationships among forest biomes. Our findings highlight the importance of ectomycorrhizal dominance in regulating multifunctionality in subtropical forests. However, this ectomycorrhizal feedback in shaping ecosystem functions cannot necessarily be generalized across forests. Therefore, we argue that the predictions for ecosystem multifunctionality in response to the shifts of mycorrhizal composition could vary across space and time.

Asunto(s)

Bosques , Micorrizas , Micorrizas/fisiología , Clima Tropical , China , Ecosistema , Modelos Biológicos , Árboles/microbiología , Árboles/fisiología , Biodiversidad , Altitud

RESUMEN

Oxathiapiprolin (OXA), which targets the oxysterol-binding protein (OSBP), is an outstanding piperidinyl thiazole isoxazoline (PTI) fungicide that can be used to control oomycetes diseases. In this study, starting from the structure of OXA, a series of novel OSBP inhibitors were designed and synthesized by introducing an indole moiety to replace the pyrazole in OXA. Finally, compound b24 was found to exhibit the highest control effect (82%) against cucumber downy mildew (CDM) in the greenhouse at a very low dosage of 0.069 mg/L, which was comparable to that of OXA (88%). Furthermore, it showed better activity against potato late blight (PLB) than other derivatives of indole. The computational results showed that the R-conformation of b24 should be the dominant conformation binding to PcOSBP. The results of the present work indicate that the 3-fluorine-indole ring is a favorable fragment to increasing the electronic energy when binding with PcOSBP. Furthermore, compound b24 could be used as a lead compound for the discovery of new OSBP inhibitors.

Asunto(s)

Fungicidas Industriales , Enfermedades de las Plantas , Fungicidas Industriales/química , Fungicidas Industriales/farmacología , Enfermedades de las Plantas/microbiología , Relación Estructura-Actividad , Indoles/química , Indoles/farmacología , Cucumis sativus/química , Cucumis sativus/microbiología , Oomicetos/efectos de los fármacos , Solanum tuberosum/química , Estructura Molecular , Simulación del Acoplamiento Molecular , Descubrimiento de Drogas , Hidrocarburos Fluorados , Pirazoles

RESUMEN

Protoporphyrinogen IX oxidase (PPO, E.C. 1.3.3.4) plays a pivotal role in chlorophyll biosynthesis in plants, making it a prime target for herbicide development. In this study, we conducted an investigation aimed at discovering PPO-inhibiting herbicides. Through this endeavor, we successfully identified a series of novel compounds based on the pyridazinone scaffold. Following structural optimization and biological assessment, compound 10ae, known as ethyl 3-((6-fluoro-5-(6-oxo-4-(trifluoromethyl)pyridazin-1(6H)-yl)benzo[d]thiazol-2-yl)thio)propanoate, emerged as a standout performer. It exhibited robust activity against Nicotiana tabacum PPO (NtPPO) with an inhibition constant (Ki) value of 0.0338 µM. Concurrently, we employed molecular simulations to obtain further insight into the binding mechanism with NtPPO. Additionally, another compound, namely, ethyl 2-((6-fluoro-5-(5-methyl-6-oxo-4-(trifluoromethyl)pyridazin-1(6H)-yl)benzo[d]thiazol-2-yl)thio)propanoate (10bh), demonstrated broad-spectrum and highly effective herbicidal properties against all six tested weeds (Leaf mustard, Chickweed, Chenopodium serotinum, Alopecurus aequalis, Poa annua, and Polypogon fugax) at the dosage of 150 g a.i./ha through postemergence application in a greenhouse. This work identified a novel lead compound (10bh) that showed good activity in vitro and excellent herbicidal activity in vivo and had promising prospects as a new PPO-inhibiting herbicide lead.

Asunto(s)

Diseño de Fármacos , Inhibidores Enzimáticos , Herbicidas , Nicotiana , Proteínas de Plantas , Protoporfirinógeno-Oxidasa , Piridazinas , Protoporfirinógeno-Oxidasa/antagonistas & inhibidores , Protoporfirinógeno-Oxidasa/metabolismo , Protoporfirinógeno-Oxidasa/química , Protoporfirinógeno-Oxidasa/genética , Piridazinas/química , Piridazinas/farmacología , Herbicidas/farmacología , Herbicidas/química , Herbicidas/síntesis química , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/síntesis química , Relación Estructura-Actividad , Nicotiana/metabolismo , Nicotiana/enzimología , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Proteínas de Plantas/antagonistas & inhibidores , Proteínas de Plantas/genética , Simulación del Acoplamiento Molecular , Estructura Molecular , Malezas/efectos de los fármacos , Malezas/enzimología , Cinética

RESUMEN

Painful stimuli elicit first-line reflexive defensive reactions and, in many cases, also evoke second-line recuperative behaviors, the latter of which reflects the sensing of tissue damage and the alleviation of suffering. The lateral parabrachial nucleus (lPBN), composed of external- (elPBN), dorsal- (dlPBN), and central/superior-subnuclei (jointly referred to as slPBN), receives sensory inputs from spinal projection neurons and plays important roles in processing affective information from external threats and body integrity disruption. However, the organizational rules of lPBN neurons that provoke diverse behaviors in response to different painful stimuli from cutaneous and deep tissues remain unclear. In this study, we used region-specific neuronal depletion or silencing approaches combined with a battery of behavioral assays to show that slPBN neurons expressing substance P receptor ( NK1R) (lPBN NK1R) are crucial for driving pain-associated self-care behaviors evoked by sustained noxious thermal and mechanical stimuli applied to skin or bone/muscle, while elPBN neurons are dispensable for driving such reactions. Notably, lPBN NK1R neurons are specifically required for forming sustained somatic pain-induced negative teaching signals and aversive memory but are not necessary for fear-learning or escape behaviors elicited by external threats. Lastly, both lPBN NK1R and elPBN neurons contribute to chemical irritant-induced nocifensive reactions. Our results reveal the functional organization of parabrachial substrates that drive distinct behavioral outcomes in response to sustained pain versus external danger under physiological conditions.

Asunto(s)

Nocicepción , Núcleos Parabraquiales , Animales , Núcleos Parabraquiales/fisiología , Ratones , Nocicepción/fisiología , Neuronas/fisiología , Dolor/fisiopatología , Masculino , Conducta Animal/fisiología

RESUMEN

Feralization is an important evolutionary process, but the mechanisms behind it remain poorly understood. Here, we use the ancient fiber crop ramie (Boehmeria nivea (L.) Gaudich.) as a model to investigate genomic changes associated with both domestication and feralization. We first produced a chromosome-scale de novo genome assembly of feral ramie and investigated structural variations between feral and domesticated ramie genomes. Next, we gathered 915 accessions from 23 countries, comprising cultivars, major landraces, feral populations, and the wild progenitor. Based on whole-genome resequencing of these accessions, we constructed the most comprehensive ramie genomic variation map to date. Phylogenetic, demographic, and admixture signal detection analyses indicated that feral ramie is of exoferal or exo-endo origin, i.e., descended from hybridization between domesticated ramie and the wild progenitor or ancient landraces. Feral ramie has higher genetic diversity than wild or domesticated ramie, and genomic regions affected by natural selection during feralization differ from those under selection during domestication. Ecological analyses showed that feral and domesticated ramie have similar ecological niches that differ substantially from the niche of the wild progenitor, and three environmental variables are associated with habitat-specific adaptation in feral ramie. These findings advance our understanding of feralization, providing a scientific basis for the excavation of new crop germplasm resources and offering novel insights into the evolution of feralization in nature.

Asunto(s)

Boehmeria , Variación Genética , Genoma de Planta , Boehmeria/genética , Productos Agrícolas/genética , Domesticación , Adaptación Fisiológica/genética , Filogenia

Asunto(s)

Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/cirugía , Meningioma/patología , Meningioma/diagnóstico por imagen , Neoplasias Meníngeas/patología , Neoplasias Meníngeas/diagnóstico por imagen , Neoplasias Meníngeas/cirugía , Neoplasias Meníngeas/complicaciones , Femenino , Persona de Mediana Edad , Masculino , Lóbulo Frontal/diagnóstico por imagen

RESUMEN

Drug discovery often begins with a new target. Protein-protein interactions (PPIs) are crucial to multitudinous cellular processes and offer a promising avenue for drug-target discovery. PPIs are characterized by multi-level complexity: at the protein level, interaction networks can be used to identify potential targets, whereas at the residue level, the details of the interactions of individual PPIs can be used to examine a target's druggability. Much great progress has been made in target discovery through multi-level PPI-related computational approaches, but these resources have not been fully discussed. Here, we systematically survey bioinformatics tools for identifying and assessing potential drug targets, examining their characteristics, limitations and applications. This work will aid the integration of the broader protein-to-network context with the analysis of detailed binding mechanisms to support the discovery of drug targets.

Asunto(s)

Biología Computacional , Descubrimiento de Drogas , Descubrimiento de Drogas/métodos , Biología Computacional/métodos , Humanos , Proteínas/metabolismo , Mapas de Interacción de Proteínas/efectos de los fármacos , Mapeo de Interacción de Proteínas/métodos , Unión Proteica

Asunto(s)

Neoplasias Cerebelosas , Ángulo Pontocerebeloso , Tumores Fibrosos Solitarios , Humanos , Tumores Fibrosos Solitarios/cirugía , Tumores Fibrosos Solitarios/patología , Tumores Fibrosos Solitarios/diagnóstico por imagen , Ángulo Pontocerebeloso/patología , Ángulo Pontocerebeloso/diagnóstico por imagen , Neoplasias Cerebelosas/patología , Neoplasias Cerebelosas/diagnóstico por imagen , Neoplasias Cerebelosas/cirugía , Masculino , Femenino , Persona de Mediana Edad , Imagen por Resonancia Magnética

RESUMEN

Homogentisate solanesyltransferase (HST) is a crucial enzyme in the plastoquinone biosynthetic pathway and has recently emerged as a promising target for herbicides. In this study, we successfully expressed and purified a stable and highly pure form of seven times transmembrane protein Chlamydomonas reinhardtii HST (CrHST). The final yield of CrHST protein obtained was 12.2 mg per liter of M9 medium. We evaluated the inhibitory effect on CrHST using Des-Morpholinocarbony Cyclopyrimorate (DMC) and found its IC50 value to be 3.63 ± 0.53 µM, indicating significant inhibitory potential. Additionally, we investigated the substrate affinity of CrHST with two substrates, determining the Km values as 22.76 ± 1.70 µM for FPP and 48.54 ± 3.89 µM for HGA. Through sequence alignment analyses and three-dimensional structure predictions, we identified conserved amino acid residues forming the active cavity in the enzyme. The results from molecular docking and binding energy calculations indicate that DMC has a greater binding affinity with HST compared to HGA. These findings represent substantial progress in understanding CrHST's properties and potential for herbicide development. KEY POINTS: • First high-yield transmembrane CrHST protein via E. coli system • Preliminarily identified active cavity composition via activity testing • Determined substrate and inhibitor modes via molecular docking.

Asunto(s)

Chlamydomonas reinhardtii , Herbicidas , Escherichia coli/genética , Simulación del Acoplamiento Molecular , Proteínas de la Membrana , Aminoácidos , Chlamydomonas reinhardtii/genética , Herbicidas/farmacología , Fenilacetatos

RESUMEN

Fosmidomycin (FOS) is a natural product inhibiting the DXR enzyme in the MEP pathway and has stimulated interest for finding more suitable FOS analogues. Herein, two series of FOS analogue hydroxamate-containing bisphosphonates as proherbicides were designed, with bisphosphonate replacing the phosphonic unit in FOS while retaining the hydroxamate (BPF series) or replacing it with retro-hydroxamate (BPRF series). The BPF series were synthesized through a three-step reaction sequence including Michael addition of vinylidenebisphosphonate, N-acylation, and deprotection, and the BPRF series were synthesized with a retro-Claisen condensation incorporated into the reaction sequence. Evaluation on model plants demonstrated several compounds having considerable herbicidal activities, and in particular, compound 8m exhibited multifold activity enhancement as compared to the control FOS. The proherbicide properties were comparatively validated. Furthermore, DXR enzyme assay, dimethylallyl pyrophosphate rescue, and molecular docking verified 8m to be a promising proherbicide candidate targeting the DXR enzyme. In addition, 8m also displayed good antimalarial activities.

Asunto(s)

Isomerasas Aldosa-Cetosa , Antimaláricos , Fosfomicina , Fosfomicina/análogos & derivados , Difosfonatos , Simulación del Acoplamiento Molecular , Fosfomicina/farmacología , Isomerasas Aldosa-Cetosa/metabolismo

RESUMEN

Plant polysaccharides, distinguished by diverse glycosidic bonds and various cyclic sugar units, constitute a subclass of primary metabolites ubiquitously found in nature. Contrary to common understanding, plant polysaccharides typically form hydrocolloids upon dissolution in water, even though both excessively high and low temperatures impede this process. Bletilla striata polysaccharides (BSP), chosen for this kinetic study due to their regular repeating units, help elucidate the relationship between polysaccharide gelation and temperature. It is suggested that elevated temperatures enhance the mobility of BSP molecular chains, resulting in a notable acceleration of hydrogen bond breakage between BSP and water molecules and consequently, compromising the conformational stability of BSPs to some extent. This study unveils the unique relationship between polysaccharide dissolution processes and temperature from a kinetics perspective. Consequently, the conclusion provides a dynamical basis for comprehending the extraction and preparation of natural plant polysaccharide hydrocolloids, pharmaceuticals and related fields.

Asunto(s)

Coloides , Simulación de Dinámica Molecular , Orchidaceae , Polisacáridos , Polisacáridos/química , Coloides/química , Orchidaceae/química , Temperatura , Agua/química , Cinética , Enlace de Hidrógeno

RESUMEN

Picolinamide fungicides, structurally related to UK-2A and antimycin-A, bind into the Qi-site in the bc1 complex. However, the detailed binding mode of picolinamide fungicides remains unknown. In the present study, antimycin-A and UK-2A were selected to study the binding mode of picolinamide inhibitors with four protonation states in the Qi-site by integrating molecular dynamics simulation, molecular docking, and molecular mechanics Generalized Born surface area (MM/GBSA) calculations. Subsequently, a series of new picolinamide derivatives were designed and synthesized to further understand the effects of substituents on the tail phenyl ring. The computational results indicated that the substituted aromatic rings in antimycin-A and UK-2A were the pharmacophore fragments and made the primary contribution when bound to a protein. Compound 9g-hydrolysis formed H-bonds with Hie201 and Ash228 and showed an IC50 value of 6.05 ± 0.24 µM against the porcine bc1 complex. Compound 9c, with a simpler chemical structure, showed higher control effects than florylpicoxamid against cucumber downy mildew and expanded the fungicidal spectrum of picolinamide fungicides. The structural and mechanistic insights obtained from the present study will provide a valuable clue for the future designing of new promising Qi-site inhibitors.

Asunto(s)

Antimicina A/análogos & derivados , Fungicidas Industriales , Ácidos Picolínicos , Animales , Porcinos , Fungicidas Industriales/farmacología , Simulación del Acoplamiento Molecular , Citocromos , Complejo III de Transporte de Electrones , Lactonas , Piridinas

RESUMEN

4-Hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) is one of the most valuable herbicide targets due to its unique biological functions. In search of HPPD inhibitors with promising biological performance, we designed and synthesized a series of novel tetrazolamide-benzimidazol-2-ones using a structure-based drug design strategy. Among the synthesized compounds, 1-(2-chlorobenzyl)-3-methyl-N-(1-methyl-1H-tetrazol-5-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-4-carboxamide, 25, IC50 = 10 nM, was identified to be the most outstanding HPPD inhibitor, which showed more than 36-fold increased Arabidopsis thaliana HPPD (AtHPPD) inhibition potency than mesotrione (IC50 = 363 nM). Our AtHPPD-25 complex indicated that one nitrogen atom on the tetrazole ring and the oxygen atom on the amide group formed a classical bidentate chelation interaction with the metal ion, the benzimidazol-2-one ring created a tight π-π stacking interaction with Phe381 and Phe424, and some hydrophobic interactions were also found between the ortho-Cl-benzyl group and surrounding residues. Compound 32 showed more than 80% inhibition against all four tested weeds at 150 g ai/ha by the postemergence application. Our results indicated that the tetrazolamide-benzimidazol-2-one scaffold may be a new lead structure for herbicide discovery.

Asunto(s)

4-Hidroxifenilpiruvato Dioxigenasa , Arabidopsis , Bencimidazoles , Herbicidas , Estructura Molecular , Relación Estructura-Actividad , 4-Hidroxifenilpiruvato Dioxigenasa/química , Herbicidas/farmacología , Herbicidas/química , Arabidopsis/metabolismo , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química

RESUMEN

Background: Modicella Kanouse (1936) is the only genus of Mortierellaceae known to produce macroscopic fruiting bodies in the form of small, whitish, round sporocarps. Specimens which belong to Modicella were collected during our field investigations in tropical karst areas of China. Based on morphological characteristics and phylogenetic analysis, a new species is introduced. New information: Modicellaguangxiensis is described as a new species from tropical karst areas of China. The main distinguishing characteristics of M.guangxiensis are the number of sporangiospores per sporangium (11-18), the size of sporangiospores (14-34 × 12-27.5 µm) and the surface of some hyphae with hemispherical tuber. The phylogenetic analyses, based on the internal transcribed spacer (ITS) and the large subunit (LSU) regions of rDNA sequences using Bayesian (BA) and Maximum Likelihood (ML) methods showed that the new taxon is closely related to M.reniformis.