@Article{or.2022.03570,
AUTHOR = {HASSAN M. OTIFI, MISHARI ALSHYARBA, MAJED AL FAYI, AYED A. DERA, PRASANNA RAJAGOPALAN},
TITLE = {Computational docking and <i>in vitro</i> analysis identifies novel arylidene analogue FPMXY-14 against renal cancer cells by attenuating Akt},
JOURNAL = {Oncology Research},
VOLUME = {29},
YEAR = {2021},
NUMBER = {3},
PAGES = {217--227},
URL = {http://www.techscience.com/or/v29n3/49189},
ISSN = {1555-3906},
ABSTRACT = {Targeted therapies are gaining global attention to tackle Renal Cancer (RC). This study aims to screen FPMXY-
14 (novel arylidene analogue) for Akt inhibition by computational and <i>in vitro</i> methods. FPMXY-14 was subjected to
proton NMR analysis and Mass spectrum analysis. Vero, HEK-293, Caki-1, and A498 cell lines were used. Akt
enzyme inhibition was studied with the fluorescent-based kit assay. Modeller 9.19, Schrodinger 2018-1, LigPrep
module, and Glide docking were used in computational analysis. The nuclear status was assessed by PI/Hoechst-
333258 staining, cell cycle, and apoptosis assays were performed using flow cytometry. Scratch wound and migrations
assays were performed. Western blotting was applied to study key signalling proteins. FPMXY-14 selectively inhibited
kidney cancer cell proliferation with GI<sub>50</sub> values of 77.5 nM and 101.40 nM in Caki-1 cells and A-498 cells,
respectively. The compound dose-dependently inhibited Akt enzyme with an IC<sub>50</sub> value of 148.5 nM and bound
efficiently at the allosteric pocking of the Akt when computationally analyzed. FPMXY-14 caused nuclear
condensation/fragmentation, increased the sub G<sub>0</sub>/G<sub>1</sub>, G<sub>2</sub>M populations, and induced early, late phase apoptosis in
both cells when compared to controls. Treatment of the compound inhibited wound healing and migration of tumor
cells, while proteins like Bcl-2, Bax, and caspase 3 were also altered. FPMXY-14 effectively inhibited the
phosphorylation of Akt in these cancer cells, while total Akt was unaltered. FPMXY-14 exhibited anti-proliferative
and anti-metastatic activities in kidney cancer cells by attenuating the Akt enzyme. Further pre-clinical research on
animals with a detailed pathway elucidation is recommended.},
DOI = {10.32604/or.2022.03570}
}