RESUMO
A series of novel N-substituted hydrazide derivatives were synthesized by reacting atranorin, a compound with a natural depside structure (1), with a range of hydrazines. The natural product and 12 new analogues (2-13) were investigated for inhibition of α-glucosidase. The N-substituted hydrazide derivatives showed more potent inhibition than the original. The experimental results were confirmed by docking analysis. This study suggests that these compounds are promising molecules for diabetes therapy. Molecular dynamics simulations were carried out with compound 2 demonstrating the best docking model using Gromac during simulation up to 20 ns to explore the stability of the complex ligand-protein. Furthermore, the activity of all synthetic compounds 2-13 against a normal cell line HEK293, used for assessing their cytotoxicity, was evaluated.
Assuntos
Inibidores de Glicosídeo Hidrolases/síntese química , Hidroxibenzoatos/química , Hipoglicemiantes/química , alfa-Glucosidases/metabolismo , Sítios de Ligação , Domínio Catalítico , Sobrevivência Celular/efeitos dos fármacos , Inibidores de Glicosídeo Hidrolases/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Células HEK293 , Humanos , Hidrazinas/química , Hidroxibenzoatos/metabolismo , Hidroxibenzoatos/farmacologia , Hipoglicemiantes/metabolismo , Hipoglicemiantes/farmacologia , Conformação Molecular , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , alfa-Glucosidases/químicaRESUMO
A facile approach was employed to fabricate MIL-100(Fe) materials from Fe2O3 nanoparticles through a conventional hydrothermal reaction without the presence of HF and HNO3. Effects of trimesic acid content in the reaction system on the quality and CO2/N2 separation performance of the as-prepared MIL-100(Fe) samples were investigated. Using 1.80 g of trimesic acid in the reaction system yielded the sample M-100Fe@Fe2O3#1.80, which proved to be the optimal sample. This choice struck a balance between the amount of required trimesic acid and the quality of the resulting material, resulting in a high yield of 81% and an impressive BET surface area of 1365.4 m2·g-1. At 25 °C and 1 bar, M-100Fe@Fe2O3#1.80 showed a CO2 adsorption capacity of 1.10 mmol·g-1 and an IAST-predicted CO2/N2 selectivity of 18, outperforming conventional adsorbents in CO2/N2 separation. Importantly, this route opens a new approach to utilizing Fe2O3-based waste materials from the iron and steel industry in manufacturing Fe-based MIL-100 materials.