Novel furo[2,3-<i>d</i>]pyrimidine derivatives as PI3K/AKT dual inhibitors: design, synthesis, biological evaluation, and molecular dynamics simulation

Abstract

= 0.175 ± 0.007, 0.071 ± 0.003 and 0.411 ± 0.02 μM, respectively. Additionally, it could strongly induce cell cycle arrest in breast cancer HS 578T cells at the G0-G1 phase and trigger apoptosis. Molecular docking and dynamics were also performed in this study which revealed that compound 10b provided an improved binding pattern with the key amino acids in the PI3K and AKT-1 binding sites. According to the findings, the designed compound 10b has potent antiproliferative and apoptotic activities with a wide therapeutic index particularly against breast cancer.