RESUMO
A convenient microwave-assisted one-pot four-component synthetic approach was developed en route to novel functionalized benzo[a]pyridazino[3,4-c]phenazine derivatives starting from 2-hydroxy-1,4-naphthoquinone, aromatic aldehydes, methyl hydrazine and o-phenylenediamine. Nine new derivatives were successfully synthesized and subsequently evaluated in terms of their biological profiles. The results revealed good cytotoxic activities of compounds 6a, 6h against KB, HepG2, Lu1 and MCF7 human cancer cell lines. Besides that, compound 6d exhibited promising antimicrobial activities toward Staphylococcuc aureus and Bacillus subtilis bacterial strains with IC50 < 6 µM.
Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Fenazinas/farmacologia , Piridazinas/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/síntese química , Antibacterianos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Fenazinas/síntese química , Fenazinas/química , Piridazinas/síntese química , Piridazinas/química , Relação Estrutura-AtividadeRESUMO
A library of twelve quinazoline-triazole hybrid compounds were designed, synthesized and evaluated as a novel class of acetylcholinesterase inhibitors to treat Alzheimer's disease (AD). The biological assay results demonstrated the ability of several hybrid compounds to inhibit AChE enzyme (IC50 range = 0.2-83.9 µM). To understand the high potential activity of these compounds, molecular docking simulations were performed to get better insights into the mechanism of binding of quinazoline-triazole hybrid compounds. As expected, compounds 8a and 9a-b bind to both catalytic anionic site (CAS) and peripheral anionic site (PAS) in the active site of AChE enzyme, which implicates that these compounds could act as dual binding site inhibitors. These compounds were not cytotoxic and they also displayed appropriated physicochemical as well as pharmacokinetic profile to be developed as novel anti-AD drug candidates.
