RESUMO
A library of 6-(((1-(substitutedphenyl)-1H-1,2,3-triazol-4-yl)methyl) amino)-3-methylquinazolin-4(3H)-one analogues synthesized from Isatin precursor through a series of nitration, reduction, hydrolysis, cyclization and click reaction. The structures of compounds were characterized by spectral data including IR, 1 H-NMR, 13 C NMR and Mass. The novel quinazolinone - 1,2,3-triazoles were screened for their cytotoxicity against the human breast adenocarcinoma cell lines MCF-7 by MTT assay. 4-Isopropyl and 2-bromo substituted analogues executed high activity against MCF-7â cell line with IC50 value of 10.16±0.07â µM and 11.23±0.20â µM compared to the Doxorubicin whose IC50 value is 10.81±0.03â µM. The activity of remaining compounds is good to moderate. Further, the molecular docking studies against the crystal structure of Epidermal Growth Factor Receptor delivered the best binding energies and the interactions such as H-bond and hydrophobic are inevitable. The predicted pharmacokinetic properties results showed that these compounds have more drug likeness properties.
Assuntos
Antineoplásicos , Triazóis , Humanos , Células MCF-7 , Estrutura Molecular , Relação Estrutura-Atividade , Triazóis/química , Quinazolinonas/farmacologia , Quinazolinonas/química , Antineoplásicos/química , Linhagem Celular Tumoral , Simulação de Acoplamento Molecular , Proliferação de CélulasRESUMO
We describe the first examples of small molecules able to disrupt the nanomolar interaction between the pro-apoptotic protein PUMA and its anti-apoptotic counterpart BcL-xL in malignant cells. Based on molecular modelling studies, we propose a rationale to this result, through a new "bottle-opener"-type strategy which could be of general use in the area of protein-protein interaction studies.