{Reference Type}: Journal Article
{Title}: Natural inspired piperine-based ureas and amides as novel antitumor agents towards breast cancer.
{Author}: Elimam DM;Elgazar AA;El-Senduny FF;El-Domany RA;Badria FA;Eldehna WM;
{Journal}: J Enzyme Inhib Med Chem
{Volume}: 37
{Issue}: 1
{Year}: Dec 2022
{Factor}: 5.756
{DOI}: 10.1080/14756366.2021.1988944
{Abstract}: In this work, the natural piperine moiety was utilised to develop two sets of piperine-based amides (5a-i) and ureas (8a-y) as potential anticancer agents. The anticancer action was assessed against triple negative breast cancer (TNBC) MDA-MB-231, ovarian A2780CP and hepatocellular HepG2 cancer cell lines. In particular, 8q stood out as the most potent anti-proliferative analogue against TNBC MDA-MB-231 cells with IC50 equals 18.7 µM, which is better than that of piperine (IC50 = 47.8 µM) and 5-FU (IC50 = 38.5 µM). Furthermore, 8q was investigated for its possible mechanism of action in MDA-MB-231 cells via Annexin V-FITC apoptosis assay and cell cycle analysis. Moreover, an in-silico analysis has proposed VEGFR-2 as a probable enzymatic target for piperine-based derivatives, and then has explored the binding interactions within VEGFR-2 active site (PDB:4ASD). Finally, an in vitro VEGFR-2 inhibition assay was performed to validate the in silico findings, where 8q showed good VEGFR-2 inhibitory activity with IC50 = 231 nM.