%0 Journal Article
%T Design and synthesis of phthalazine-based compounds as potent anticancer agents with potential antiangiogenic activity via VEGFR-2 inhibition
%A Asmaa M. Aboul-Magd
%A Deena S. Lasheen
%A Khaled A. M. Abouzid
%A Salwa Elmeligie
%A Sohair M. Khojah
%A Tamer M. Abdelghany
%A Tamer M. Ibrahim
%J Journal of Enzyme Inhibition and Medicinal Chemistry
%D 2019
%R https://doi.org/10.1080/14756366.2019.1642883
%X Abstract In the designed compounds, either a biarylamide or biarylurea moiety or an N-substituted piperazine motif was linked to position 1 of the phthalazine core. The anti-proliferative activity of the synthesised compounds revealed that eight compounds (6b, 6e, 7b, 13a, 13c, 16a, 16d and 17a) exhibited excellent broad spectrum cytotoxic activity in NCI 5-log dose assays against the full 60 cell panel with GI50 values ranging from 0.15 to 8.41£¿¦ÌM. Moreover, the enzymatic assessment of the synthesised compounds against VEGFR-2 tyrosine kinase showed the significant inhibitory activities of the biarylureas (12b, 12c and 13c) with IC50s of 4.4, 2.7 and 2.5£¿¦ÌM, respectively, and with 79.83, 72.58 and 71.6% inhibition of HUVEC at 10£¿¦ÌM, respectively. Additionally, compounds (7b, 13c and 16a) were found to induce cell cycle arrest at S phase boundary. Compound 7b triggered a concurrent increase in cleaved caspase-3 expression level, indicating the apoptotic-induced cell death
%U https://www.tandfonline.com/doi/full/10.1080/14756366.2019.1642883