RESUMO
Aldose reductase (ALR2) inhibitors provide a viable mode to fight against diabetic complications. ALR2 exhibit plasticity in the active site vicinities and possible shifts in the nearby two supporting alpha helices. Therefore, a novel series of amino acid conjugates of chromene-3-imidazoles (13-15) were designed and synthesized based on natural isoflavonoids. The compounds were identified on the basis of spectral (1H NMR, 13C NMR and MS) data and tested in vitro for ALR2 inhibitory activity with an IC50 value ranges from 0.031 ± 0.082 µM to 4.29 ± 0.55 µM. Our in silico and biochemical studies confirmed that 15e has the best inhibition activity among the synthesized compounds with a high selective index against the Aldehyde reductase (ALR1). Supplementation of 15e to STZ induced rats decreased the blood glucose levels and delayed the progression of cataract in a dose-dependent manner. The present study thus provides novel series of compounds with a promising inhibitor to prevent or delay the cataract progression.
Assuntos
Aldeído Redutase/antagonistas & inibidores , Aminoácidos/síntese química , Aminoácidos/farmacologia , Desenho de Fármacos , Imidazóis/química , Aminoácidos/química , Animais , Benzopiranos/síntese química , Benzopiranos/química , Benzopiranos/farmacologia , Glicemia/efeitos dos fármacos , Domínio Catalítico , Catarata/tratamento farmacológico , Catarata/etiologia , Complicações do Diabetes/tratamento farmacológico , Modelos Animais de Doenças , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Imidazóis/síntese química , Imidazóis/farmacologia , Concentração Inibidora 50 , Simulação de Acoplamento Molecular , Ratos , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
Taking into consideration of the biological activity of betulinic acid derivatives containing a oxadiazole ring, the semisynthetic betulinic acid-1,2,4-oxadiazole esters (14-25) were synthesized starting from betulinic acid (1) and 5-(bromomethyl)-3-aryl-1,2,4-oxadiazoles (2-13) and final compounds were tested for cytotoxic activity on three human cancer cell lines in vitro. All tested compounds showed good cytotoxic activity. The structures of synthesized compounds are established based on infrared (IR), nuclear magnetic resonance (NMR), and mass spectrometry.
Assuntos
Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Oxidiazóis/química , Oxidiazóis/farmacologia , Triterpenos/química , Antineoplásicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Oxidiazóis/síntese química , Triterpenos Pentacíclicos , Relação Estrutura-Atividade , Ácido BetulínicoRESUMO
A new furoquinoline alkaloid, 5-hydroxydictamnine, along with ß-sitosterol was isolated from the heartwood of Atalantia monophylla. The structure of this alkaloid was established by chemical and spectral evidences together with a nuclear overhauser effect (NOE) experiment.
Assuntos
Alcaloides/isolamento & purificação , Quinolinas/isolamento & purificação , Rutaceae/química , Alcaloides/química , Estrutura Molecular , Plantas Medicinais/química , Quinolinas/química , Sitosteroides/isolamento & purificação , Madeira/químicaRESUMO
An unusual novel and significant anti-oxidant 1,2-dibenzoyl glycoside, natansnin (1), has been isolated from Salvinia natans. The structure of 1 was established by the study of NMR and CD spectral data.
