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

Molecules · 7 authors, 4 centres

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AGENT 01 · STRUCTURED SUMMARY

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TL;DR

Compound 11 showed reduced expression of the cancer-related gene mTOR and had a good predicted drug-like profile.

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603 CHARS

A series of novel 2-phenylamino-3-acyl-1,4-naphthoquinones were synthesized and evaluated for antiproliferative activity in vitro against DU-145 (prostate), MCF-7 (breast), and T24 (bladder) human cancer cell lines. In silico analyses suggested compound 11 has favorable drug-like properties. In DU-145 cells, compound 11 significantly reduced the expression of the mTOR gene, which is involved in tumor metabolism, and molecular docking indicated it has good affinity for the mTOR protein. The authors propose compound 11 inhibits cancer cell proliferation through reduced mTOR expression and activity.

STUDY TYPE

other

SPECIALTY

oncology

SUMMARISED BY

AI pipeline

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100% · A

ORIGINAL PAPER

PMC10254843

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

Molecules

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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 such as half-wave potentials, hydrophobicity and molar refractivity. Compounds 4 and 11 displayed the highest antiproliferative activity against the three cancer cells and were therefore further investigated. 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. Moreover, the expressions of key genes were 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 shows 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.

CITATION EXPORT

Julio Benites, Jaime A. Valderrama, Álvaro Contreras et al.. 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. Molecules. (2023). https://doi.org/10.3390/molecules28114323

AUTHORS

7 · 4 CENTRES

Julio Benites, Jaime A. Valderrama, Álvaro Contreras, Cinthya Enríquez, Ricardo Pino-Rios, Osvaldo Yáñez, Pedro Buc Calderon

1Química y Farmacia, Facultad de Ciencias de la Salud, Universidad Arturo Prat, Casilla 121, Iquique 1100000, Chile; [email protected] (J.B.); [email protected] (J.A.V.); [email protected] (Á.C.); [email protected] (C.E.); [email protected] (R.P.-R.)
2Departamento de Química Orgánica, Facultad de Química y de Farmacia, Pontificia Universidad Católica de Chile, Avenida Vicuña Mackenna 4860, Santiago 7820436, Chile
3Núcleo de Investigación en Data Science, Facultad de Ingeniería y Negocios, Universidad de las Américas, Santiago 7500000, Chile; [email protected]
4Research Group in Metabolism and Nutrition, Louvain Drug Research Institute, Université Catholique de Louvain, 73 Avenue E. Mounier, 1200 Brussels, Belgium

EDITOR / REVIEWER

Qiao-Hong Chen