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,Yasser H Zaki,Ahmed Elhenawy,Adil Aldhahrani,Ayman A Swelum,Omar M Ali,Hamada H Amer

doi:10.3390/molecules27030756

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.

Highlights

Introduction distributed under the terms andThere are lots of compounds which have therapeutic effects, such as α-Aminophosphonates, which have different biological activities such as antibacterial [1], anti-alzheimer disease [2], anti-tumor [3], and anticancer activity [4]
Our study aims to study the effect of α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin2(1H)-one on DMBA model of breast cancer in albino rats with insilico prediction of their thymidylate synthase inhibitory effect
Benzaldhyde 1 was reacted with acetone 2 under reflux in the presence of sodium hydroxide in absolute ethanol to give dibenzalacetone 3, which reacted with hydrazine hydrate and formic acid under reflux to give 5-phenyl-3-styryl-4,5-dihydro-1H-pyrazole1-carbaldehyde 4, which reacted with amine derivatives 5a, b and triphenyl phosphite

Summary

Introduction

There are lots of compounds which have therapeutic effects, such as α-Aminophosphonates, which have different biological activities such as antibacterial [1], anti-alzheimer disease [2], anti-tumor [3], and anticancer activity [4]. A new compound of phosphonates has been designed, synthesized and tested, diethyl 3-nonyl-5-oxo-3,5,6,6 a-tetrahydro-1H-cyclopenta conditions of the Creative Commons. It has been tested in-vitro for its anti-inflammatory effects and in-vivo for its ability to improve colitis [5]. In vitro tests showed excellent COX-2 inhibitory activity and antiproliferative activity against MCF-7 cells, which provided some new ideas in designing therapeutic drugs for COX-2 inhibitors with selective and anti-tumor activity [7]

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