RESUMO
Tomato fruit is susceptible to chilling injury (CI) when stored at low temperatures, limiting its storage potential, and resulting in economic loss if inappropriate temperatures are used. Brassinolide (BR) is a plant growth regulator that is known to decrease the susceptibility of fruit to CI. In this study, transcriptome, metabolome, and proteome analysis revealed the regulation mechanism of BR treatment in alleviating tomato fruit CI. The results showed that the differentially expressed metabolites mainly included amino acids, organic acids, carbohydrates, and lipids. Differentially expressed genes (DEGs) were involved in plant cold stress response (HSFA3, SHSP, and TPR), fruit redox process (POD, PAL, and LOX), related to the fruit texture (CESA, ß-Gal, and PAE), plant hormone signal transduction (ACS3, ARF, and ERF,), transcription factors (TCP, bHLH, GATA). Moreover, differentially expressed proteins were associated with fruit texture (CESA, PE, PL, and CHI), plant oxidation processes (LOX, GPX, CAT, and POD), plant cold stress response (HSF, HSP20, HSP70, and HSP90B), plant hormone signal transduction (BSK1 and JAR1) and transcription factors (WRKY and MYB). Our study showed that BR alleviates CI symptoms of tomato fruit by regulating LOX in the α-linolenic acid metabolism pathway, enhancing jasmonic acid-CoA (JA-CoA) synthesis, inhibiting cell wall and membrane lipid damage. The results provided a theoretical basis for further study on the CI mechanism of tomato fruit.
RESUMO
Drug resistant tuberculosis (TB) infections are on the rise and antibiotics that inhibit Mycobacterium tuberculosis through a novel mechanism could be an important component of evolving TB therapy. Protein kinase A (PknA) and protein kinase B (PknB) are both essential serine-threonine kinases in M. tuberculosis. Given the extensive knowledge base in kinase inhibition, these enzymes present an interesting opportunity for antimycobacterial drug discovery. This study focused on targeting both PknA and PknB while improving the selectivity window over related mammalian kinases. Compounds achieved potent inhibition (Ki ≈ 5 nM) of both PknA and PknB. A binding pocket unique to mycobacterial kinases was identified. Substitutions that filled this pocket resulted in a 100-fold differential against a broad selection of mammalian kinases. Reducing lipophilicity improved antimycobacterial activity with the most potent compounds achieving minimum inhibitory concentrations ranging from 3 to 5 µM (1-2 µg/mL) against the H37Ra isolate of M. tuberculosis.
RESUMO
The (13)C NMR spectra of over 24 tetracyclic triterpenoid derivatives have been structurally analyzed. The (13)C NMR chemical shifts allow one to probe the steric topology of the rigid steroid skeleton and inductive effects of its substituents. Use of deuterium labeling in chemical shift assignment and B-ring aromatic terpenoids are also featured.
Assuntos
Lanosterol/química , Acetilação , Ácidos e Sais Biliares/química , Carbono/química , Deutério/química , Isomerismo , Espectroscopia de Ressonância MagnéticaRESUMO
An efficient and scalable synthesis of three differentially protected 2-(hydroxymethyl)piperazines is presented, starting from optically active and commercially available (2S)-piperazine-2-carboxylic acid dihydrochloride. These synthetic building blocks are useful in the preparation of biologically active compounds and as chemical scaffolds for the construction of combinatorial libraries.
Assuntos
Piperazinas/síntese química , Conformação Molecular , Estrutura Molecular , Piperazinas/químicaRESUMO
A new class of oxazolidinone antibacterials incorporating oxygen-, nitrogen-, or sulfur-containing heterobicyclic C-rings is described. The in vitro potency and in vivo efficacy of these conformationally constrained oxazolidinone analogs are discussed.
Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Compostos Aza/química , Oxazolidinonas/síntese química , Oxazolidinonas/farmacologia , Compostos de Sulfidrila/química , Amidas/química , Animais , Antibacterianos/química , Antibacterianos/uso terapêutico , Compostos Aza/síntese química , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Camundongos , Conformação Molecular , Oxazolidinonas/química , Oxazolidinonas/uso terapêutico , Relação Estrutura-AtividadeRESUMO
[reaction: see text] An efficient and stereospecific approach to the synthesis of structurally constrained aza-, oxa-, and thiabicyclo[3.1.0]hexane heterocycles has been achieved through application of the intramolecular cyclopropanation reaction of diazoacetates. The various constrained heterocycles (X = N, O, or S) are conveniently prepared from a common diol intermediate accessible from readily available cinnamyl alcohols. Application of the methodology to the synthesis of conformationally constrained oxazolidinone antibacterials is also discussed.
Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Propanóis/química , Antibacterianos/síntese química , Compostos Aza/síntese química , Catálise , Estrutura Molecular , Oxazolidinonas/síntese química , Oxazolidinonas/farmacologia , Oxigênio/química , Compostos de Enxofre/síntese químicaRESUMO
Negamycin 1 is a bactericidal antibiotic with activity against Gram-negative bacteria, and served as a template in an antibiotic discovery program. An orthogonally protected beta-amino acid derivative 3a was synthesized and used in parallel synthesis of negamycin derivatives on solid support. This advanced intermediate was also used for N- and C-terminal modifications using solution-phase methodologies. The N-terminal modifications have resulted in the identification of active analogues, whereas the C-terminal modifications resulted in complete loss of antibacterial activity. The N-methyl negamycin analogue, 19a, inhibits protein synthesis (IC(50)=2.3 microM), has antibacterial activity (Escherichia coli, MIC=16 microgram/mL), and is efficacious in an E. coli murine septicemia model (ED(50)=16.3mg/kg).
Assuntos
Diamino Aminoácidos/química , Diamino Aminoácidos/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Animais , Bactérias/efeitos dos fármacos , Proteínas de Bactérias/biossíntese , Desenho de Fármacos , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Hidrazinas/química , Indicadores e Reagentes , Camundongos , Testes de Sensibilidade Microbiana , Conformação Molecular , Inibidores da Síntese de Proteínas/síntese química , Inibidores da Síntese de Proteínas/farmacologia , Sepse/tratamento farmacológico , Sepse/microbiologiaRESUMO
X-ray crystallographic determinations and AM1 calculations have defined the solid-state and gas-phase structures of cyclotri(deoxycholate) and cyclotetra(24-norcholate). The latter cyclotetramer is one of the largest open macrocycles ever subjected to crystallography.