Novel quinoxaline-3-propanamides as VGFR-2 inhibitors and apoptosis inducers
Magda M. F. Ismail, Taghreed Z. Shawer, Rabab S. Ibrahim, Mostafa S. Abusaif, Mona M. Kamal, Rasha M. Allam, Yousry A. Ammar
Abstract
, caspase-3 p53 and BAX. When compared to the control, significant increase in the expression levels of caspase-3 from 47.88 to 423.10 and p53 from 22.19 to 345.83 pg per ml in MCF-7 cells. As well, it increased the proapoptotic protein BAX by 4.3 times while lowering the antiapoptotic marker BCL2 by 0.45 fold. Docking studies further supported the mechanism, where compound 14 showed good binding to the essential amino acids in the active site of VEGFR-2. Pharmacokinetic properties showed the privilege of these hits over sunitinib: they are not substrates of P-gp protein; this suggests that they have less chance to efflux out of the cell, committing maximum effect; and in addition, they do not allow permeation to the BBB.