RESUMO
The one-pot domino reaction of ethyl (Z)-3-amino-3-phenylacrylates with 2-amino-N-alkyl/arylbenzamides under Lewis acid catalysis was described as an effective way to construct novel spiro [pyrrole-3,2'-quinazoline] carboxylate derivatives. By combining substituted alkyl/aryl amides with spiro annulated 1H-pyrrole-2,3-diones, this method provides a novel way for producing spiro pyrrole derivatives in good to excellent yields. The current procedure has a number of benefits, including quicker reaction times, a broad tolerance range for functional groups, and the ability to synthesize 2,3-dihydroquinazolin-4(1H)-ones that are of biological importance and take part in organic transformations. This is the first use of molecular hybridization involving linking with pyrrole derivatives and dihydroquinazolin-4(1H)-ones.
RESUMO
A novel I2/TBHP mediated domino synthesis of 2-(2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl)-N-phenyl benzamides by reaction of isatins with o-amino N-aryl/alkyl benzamides was described. This was the first application of o-amino N-aryl/alkyl benzamides participating in oxidative rearrangement with isatins for synthesis of desired products. The synthesized compounds contained amide and quinazoline units and their combination resulted in molecular hybridization of two important pharmacophores. In this study, the synthesized compounds 3a-r were screened for cytotoxicity against four cancer cell lines A549, DU145, B16-F10, and HepG2 and also non-cancerous cell line CHO-K1. The compounds 3c, 3l and 3o gave promising results. The in silico molecular docking studies (PDB ID 1N37) also validated the anticancer activity of these compounds showing good binding affinity with target DNA and by acting as DNA intercalators.
