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

Breast cancer is a major cause of death in women worldwide. In this study, 60 female rats were classified into 6 groups; negative control, -aminophosphonates, arylidine derivatives of 3-acetyl-1-aminoquinolin-2( )-one, DMBA, DMBA & -aminophosphonates, and DMBA & arylidine derivatives of 3-acetyl-1-aminoquinolin-2( )-one. New -aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2( )-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 -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( )-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( )-one, whereas PIK3R1 and BAX increased in the DMBA group treated with α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2( )-one. The molecular docking postulated that the investigated compounds can inhibt the Thymidylate synthase TM due to high hydrophobicity charachter.