Investigation of the Anticancer Effect of α-Aminophosphonates and Arylidine Derivatives of 3-Acetyl-1-aminoquinolin-2(1H)-one on the DMBA Model of Breast Cancer in Albino Rats with In Silico Prediction of Their Thymidylate Synthase Inhibitory Effect

Mohamed A Nassan; Adil Aldhahrani; Hamada H Amer; Ahmed Elhenawy; Ayman A Swelum; Omar M Ali; Yasser H Zaki

doi:10.3390/molecules27030756

Investigation of the Anticancer Effect of α-Aminophosphonates and Arylidine Derivatives of 3-Acetyl-1-aminoquinolin-2(1H)-one on the DMBA Model of Breast Cancer in Albino Rats with In Silico Prediction of Their Thymidylate Synthase Inhibitory Effect

Molecules. 2022 Jan 24;27(3):756. doi: 10.3390/molecules27030756.

Authors

Mohamed A Nassan¹, Adil Aldhahrani¹, Hamada H Amer², Ahmed Elhenawy³, Ayman A Swelum^{4

5}, Omar M Ali², Yasser H Zaki^{6

7}

Affiliations

¹ Department of Clinical Laboratory Sciences, Turabah University College, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
² Department of Chemistry, Turabah University College, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
³ Department of Chemistry, Faculty of Science, Al-Azhar University, Cairo 11884, Egypt.
⁴ Department of Theriogenology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt.
⁵ Department of Animal Production, College of Food and Agriculture Sciences, King Saud University, P.O. Box 2460, Riyadh 11451, Saudi Arabia.
⁶ Department of Chemistry, Faculty of Science, Beni-Suef University, Beni Suef 62514, Egypt.
⁷ Department of Chemistry, Faculty of Science and Humanity Studies at Al-Quwayiyah, Shaqra University, Al-Quwayiyah 11961, Saudi Arabia.

Abstract

Breast cancer is a major cause of death in women worldwide. In this study, 60 female rats were classified into 6 groups; negative control, α-aminophosphonates, arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one, DMBA, DMBA & α-aminophosphonates, and DMBA & arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one. New α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one were synthesized and elucidated by different spectroscopic and elemental analysis. Histopathological examination showed marked proliferation of cancer cells in the DMBA group. Treatment with α-aminophosphonates mainly decreased tumor mass. Bcl2 expression increased in DMBA-administered rats and then declined in the treated groups, mostly with α-aminophosphonates. The level of CA15-3 markedly declined in DMBA groups treated with α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one. Gene expression of GST-P, PCNA, PDK, and PIK3CA decreased in the DMBA group treated with α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one, whereas PIK3R1 and BAX increased in the DMBA group treated with α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one. The molecular docking postulated that the investigated compounds can inhibt the Thymidylate synthase TM due to high hydrophobicity charachter.

Keywords: 3-acetyl-1-aminoquinolin-2(1H)-one; DMBA; breast cancer; thymidylate synthase; α-aminophosphonates.

MeSH terms

9,10-Dimethyl-1,2-benzanthracene
Animals
Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use*
Caco-2 Cells
Computer Simulation
Drug Evaluation, Preclinical
Female
Fishes
Humans
Mammary Neoplasms, Experimental / chemically induced
Mammary Neoplasms, Experimental / drug therapy*
Mammary Neoplasms, Experimental / pathology
Models, Molecular
Molecular Docking Simulation
Molecular Targeted Therapy / methods
Organophosphonates / chemical synthesis
Organophosphonates / chemistry
Organophosphonates / pharmacology
Organophosphonates / therapeutic use
Plant Extracts
Quinolines / chemical synthesis
Quinolines / chemistry
Quinolines / pharmacology
Quinolines / therapeutic use
Rats
Thymidylate Synthase / antagonists & inhibitors*
Thymidylate Synthase / chemistry

Substances

Antineoplastic Agents
Organophosphonates
Plant Extracts
Quinolines
9,10-Dimethyl-1,2-benzanthracene
Thymidylate Synthase