RESUMO
Daidzein is a common isoflavone, having multiple biological effects such as anti-inflammation, anti-allergy, and anti-aging. α-Tocopherol is the tocopherol isoform with the highest vitamin E activity including anti-allergic activity and anti-cancer activity. Hesperetin is a flavone, which shows potent anti-inflammatory effects. These compounds have shortcomings, i.e., water-insolubility and poor absorption after oral administration. The glycosylation of bioactive compounds can enhance their water-solubility, physicochemical stability, intestinal absorption, and biological half-life, and improve their bio- and pharmacological properties. They were transformed by cultured Nicotiana tabacum cells to 7-ß-glucoside and 7-ß-gentiobioside of daidzein, and 3'- and 7-ß-glucosides, 3',7-ß-diglucoside, and 7-ß-gentiobioside of hesperetin. Daidzein and α-tocopherol were glycosylated by galactosylation with ß-glucosidase to give 4'- and 7-ß-galactosides of daidzein, which were new compounds, and α-tocopherol 6-ß-galactoside. These nine glycosides showed higher anti-allergic activity, i.e., inhibitory activity toward histamine release from rat peritoneal mast cells, than their respective aglycones. In addition, these glycosides showed higher tyrosinase inhibitory activity than the corresponding aglycones. Glycosylation of daidzein, α-tocopherol, and hesperetin greatly improved their biological activities.
Assuntos
Antialérgicos/síntese química , Cosméticos/síntese química , Glicosídeos/síntese química , Hesperidina/síntese química , Isoflavonas/síntese química , alfa-Tocoferol/síntese química , Animais , Antialérgicos/metabolismo , Biocatálise , Técnicas de Cultura de Células , Cosméticos/metabolismo , Alimento Funcional/análise , Glicosídeos/metabolismo , Glicosilação , Hesperidina/metabolismo , Humanos , Isoflavonas/metabolismo , Masculino , Mastócitos/citologia , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Células Vegetais/metabolismo , Cultura Primária de Células , Ratos , Ratos Wistar , Solubilidade , Nicotiana/citologia , Nicotiana/metabolismo , alfa-Tocoferol/metabolismoRESUMO
The plant hormone auxin is a master regulator of plant growth and development. By regulating rates of cell division and elongation and triggering specific patterning events, indole 3-acetic acid (IAA) regulates almost every aspect of plant development. The perception of auxin involves the formation of a ternary complex consisting of an F-box protein of the TIR1/AFB family of auxin receptors, the auxin molecule, and a member the Aux/IAA family of co-repressor proteins. In this study, we identified a potent auxin antagonist, α-(phenylethyl-2-oxo)-IAA, as a lead compound for TIR1/AFB receptors by in silico virtual screening. This molecule was used as the basis for the development of a more potent TIR1 antagonist, auxinole (α-[2,4-dimethylphenylethyl-2-oxo]-IAA), using a structure-based drug design approach. Auxinole binds TIR1 to block the formation of the TIR1-IAA-Aux/IAA complex and so inhibits auxin-responsive gene expression. Molecular docking analysis indicates that the phenyl ring in auxinole would strongly interact with Phe82 of TIR1, a residue that is crucial for Aux/IAA recognition. Consistent with this predicted mode of action, auxinole competitively inhibits various auxin responses in planta. Additionally, auxinole blocks auxin responses of the moss Physcomitrella patens, suggesting activity over a broad range of species. Our works not only substantiates the utility of chemical tools for plant biology but also demonstrates a new class of small molecule inhibitor of protein-protein interactions common to mechanisms of perception of other plant hormones, such as jasmonate, gibberellin, and abscisic acid.
Assuntos
Proteínas de Arabidopsis/antagonistas & inibidores , Desenho de Fármacos , Proteínas F-Box/antagonistas & inibidores , Ácidos Indolacéticos/antagonistas & inibidores , Receptores de Superfície Celular/antagonistas & inibidores , Arabidopsis/química , Arabidopsis/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Ácidos Indolacéticos/síntese química , Ácidos Indolacéticos/química , Ácidos Indolacéticos/isolamento & purificação , Ácidos Indolacéticos/metabolismo , Ácidos Indolacéticos/farmacologia , Modelos Moleculares , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
(1S,3R)-1-Aminocyclopentane-1,3-dicarboxylic acid (ACPD), a potent agonist of metabotropic glutamate receptors, was synthesized from L-serine. The chiral quaternary center was constructed by C-H insertion of the alkylidenecarbene, this being generated by the reaction between lithiotrimethylsilyldiazomethane and the corresponding ketone.