Design, synthesis and evaluation of 4,7-disubstituted 8-methoxyquinazoline derivatives as potential cytotoxic agents targeting β-catenin/TCF4 signaling pathway.

ABSTRACT: Overactivation of Wnt/β-catenin signaling by accumulated β-catenin in the nucleus has been shown to play a crucial role in the etiology of cancer. Interaction of β-catenin with Transcription factor 4 (TCF4) is a key step for the activation of Wnt genes in response to upstream signals of the Wnt/β-catenin pathway. Hence, down regulation of Wnt/β-catenin signaling or targeting downstream events by selective β-catenin/TCF4 protein-protein interaction inhibitors could be a potential therapeutic strategy against such cancers. In this study structure-based drug design approach was followed to design novel 4,7-disubstituted 8-methoxyquinazoline-based derivatives which could act as potential cytotoxic agents inhibiting the β-catenin/TCF4 protein-protein interactions. Fifteen compounds possessing 4

SUBMITTER: Neogi K 

PROVIDER: S-EPMC8938628 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature