RESUMO
A series of 2,3-diarylindoles were synthesized via the Larock heteroannulation, and evaluated for their anticancer activity against A549 lung cancer cells. The most potent compound, PCNT13 with IC50=5.17 µM, caused the induction of two modes of programmed cell death, apoptosis and autophagy.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Indóis/farmacologia , Células A549 , Antineoplásicos/síntese química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Indóis/síntese química , Macrolídeos/farmacologia , Relação Estrutura-AtividadeRESUMO
A series of 2,3-diarylindoles were synthesized from 2-iodoaniline and unsymmetrical diarylacetylenes using the Larock heteroannulation. Diarylacetylenes bearing electron-withdrawing substituents lead to 2,3-diarylindoles with substituted phenyl moieties at the 2-position as major products, while those with electron-donating groups preferably yield indole products with substituted phenyl moieties at the 3-position. The regioisomeric product ratios exhibit a clear correlation with Hammett σ(p) values. DFT calculations reveal the origin of this effect, displaying smaller activation energy barriers for those pathways leading to the major regioisomer.