In vitro Antitumour Activity, Genotoxicity, and Antiproliferative Effects of Aminophosphonic Acid Diesters and their Synthetic Precursors

Abstract

The Schiff bases N-furfurylidene-p-toluidine and N-(4-dimethylaminobenzilidene)- p-toluidine, and the recently synthesized aminophosphonic acid diesters p-[N-methyl- (diethoxyphosphonyl)-(2-furyl)]toluidine and p-[N-methyl(diethoxyphosphonyl)-(4-dimethylaminophenyl)] toluidine were tested for in vitro antitumour activity on six human epithelial cancer cell lines. The genotoxicity and antiproliferative activity of these compounds were tested in mice. The aminophosphonates showed high in vitro antitumour activity towards the breast cancer-derived cell lines (MCF-7 and MDA-MB-231), the cervical carcinoma cell line (HeLa), and the human colon adenocarcinoma cell line (HT-29). In addition, the Schiff base N-furfurylidene-p-toluidine significantly inhibited the growth of bladder carcinoma cells (647-V) and the hepatocellular carcinoma line HepG2, and U-shaped dose-response curves were observed after treatment of 647-V and MCF-7 cells. All studied compounds had a moderate genotoxic and antiproliferative activity in vivo