Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Discovery of New 2-Phenylamino-3-Acyl-1,4-Naphthoquinones as Inhibitors of Cancer Cells Proliferation. Searching for Intra-cellular Targets Playing a Role in Cancer Cells Survival

Julio Benites
ORCID logo ,
Jaime Adolfo Valderrama
,
Álvaro Contreras
,
Cinthya Enríquez
,
Ricardo Pino-Rios
ORCID logo ,
Osvaldo Yáñez
ORCID logo ,
Pedro Buc Calderon
* ORCID logo
Version 1 : Received: 11 April 2023 / Approved: 12 April 2023 / Online: 12 April 2023 (07:57:34 CEST)

How to cite: Benites, J.; Valderrama, J.A.; Contreras, Á.; Enríquez, C.; Pino-Rios, R.; Yáñez, O.; Buc Calderon, P. Discovery of New 2-Phenylamino-3-Acyl-1,4-Naphthoquinones as Inhibitors of Cancer Cells Proliferation. Searching for Intra-cellular Targets Playing a Role in Cancer Cells Survival. Preprints 2023, 2023040254. https://doi.org/10.20944/preprints202304.0254.v1 Benites, J.; Valderrama, J.A.; Contreras, Á.; Enríquez, C.; Pino-Rios, R.; Yáñez, O.; Buc Calderon, P. Discovery of New 2-Phenylamino-3-Acyl-1,4-Naphthoquinones as Inhibitors of Cancer Cells Proliferation. Searching for Intra-cellular Targets Playing a Role in Cancer Cells Survival. Preprints 2023, 2023040254. https://doi.org/10.20944/preprints202304.0254.v1

Abstract

A series of 2-phenylamino-3-acyl-1,4-naphtoquinones were evaluated regarding their in vitro antiproliferative activities using DU-145, MCF-7 and T24 cancer cells. Such activities were discussed in terms of molecular descriptors like half-wave potentials, hydrophobicity and molar refractivity. Compounds 4 and 11 display the highest antiproliferative activity against the three cancer cells, therefore, they were subject to further studies. The in silico prediction of drug likeness, using pkCSM and SwissADME explorer online, shows that compound 11 is a suitable lead molecule to be developed. Furthermore, the expression of some key genes was studied in DU-145 cancer cells. They include genes involved in apoptosis (Bcl-2), tumor metabolism regulation (mTOR), redox homeostasis (GSR), cell cycle regulation (CDC25A), cell cycle progression (TP53), epigenetic (HDAC4), cell-cell communication (CCN2) and inflammatory pathways (TNF). Compound 11 displays an interesting profile because among these genes, mTOR was significantly less expressed as compared to control conditions. Molecular docking show that compound 11 has good affinity with mTOR, unraveling a potential inhibitory effect on this protein. Due to the key role of mTOR on tumor metabolism, we suggest that impaired DU-145 cells proliferation by compound 11 is caused by a reduced mTOR expression (less mTOR protein) and inhibitory activity on mTOR protein.

Keywords

cancer cells; quinones; mTOR; antiproliferative activity; molecular descriptors; molecular docking

Subject

Biology and Life Sciences, Toxicology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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