Design, synthesis, apoptotic, and antiproliferative effects of 5-chloro-3- (2-methoxyvinyl)-indole-2-carboxamides and pyrido[3,4-b]indol-1-ones as potent EGFR^WT/EGFR^T790M inhibitors.

ABSTRACT: A new series of indole-2-carboxamides 5a-g, 6a-f and pyrido[3,4-b]indol-1-ones 7a and 7b have been developed as new antiproliferative agents that target both wild and mutant type EGFR. The antiproliferative effect of the new compounds was studied. 5c, 5d, 5f, 5 g, 6e, and 6f have the highest antiproliferative activity with GI₅₀ values ranging from 29 nM to 47 nM in comparison to the reference erlotinib (GI₅₀ = 33 nM). Compounds 5d, 5f, and 5 g inhibited EGFR^WT with IC₅₀ values ranging from 68 to 85 nM while the GI₅₀ of erlotinib is 80 nM. Moreover, compounds 5f and 5 g had the most potent inhibitory activity against EGFR^T790M</

SUBMITTER: Al-Wahaibi LH 

PROVIDER: S-EPMC10234138 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature