Open Access iconOpen Access

ARTICLE

Computational docking and in vitro analysis identifies novel arylidene analogue FPMXY-14 against renal cancer cells by attenuating Akt

HASSAN M. OTIFI1, MISHARI ALSHYARBA2, MAJED AL FAYI3,4, AYED A. DERA3,4, PRASANNA RAJAGOPALAN3,4,*

1 Department of Pathology, College of Medicine, King Khalid University, Abha, Saudi Arabia
2 Department of Surgery, College of Medicine, King Khalid University, Abha, Saudi Arabia
3 Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
4 Central Research Laboratory, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia

* Corresponding Author: Prasanna Rajagopalan, email

Oncology Research 2021, 29(3), 217-227. https://doi.org/10.32604/or.2022.03570

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 in vitro 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 GI50 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 IC50 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 G0/G1, G2M 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.

Keywords


Cite This Article

APA Style
OTIFI, H.M., ALSHYARBA, M., FAYI, M.A., DERA, A.A., RAJAGOPALAN, P. (2021). Computational docking and in vitro analysis identifies novel arylidene analogue FPMXY-14 against renal cancer cells by attenuating akt. Oncology Research, 29(3), 217-227. https://doi.org/10.32604/or.2022.03570
Vancouver Style
OTIFI HM, ALSHYARBA M, FAYI MA, DERA AA, RAJAGOPALAN P. Computational docking and in vitro analysis identifies novel arylidene analogue FPMXY-14 against renal cancer cells by attenuating akt. Oncol Res. 2021;29(3):217-227 https://doi.org/10.32604/or.2022.03570
IEEE Style
H.M. OTIFI, M. ALSHYARBA, M.A. FAYI, A.A. DERA, and P. RAJAGOPALAN "Computational docking and in vitro analysis identifies novel arylidene analogue FPMXY-14 against renal cancer cells by attenuating Akt," Oncol. Res., vol. 29, no. 3, pp. 217-227. 2021. https://doi.org/10.32604/or.2022.03570



cc This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
  • 1055

    View

  • 667

    Download

  • 0

    Like

Share Link