Synthesis, X-ray crystal structure, DNA/protein binding and cytotoxicity studies of five α-aminophosphonate N-derivatives

Abstract

Five new α-aminophosphonates are synthesized and characterized by EA, FT-IR, 1H NMR, 13C NMR, 31P NMR, ESI-MS and X-ray crystallography. The X-ray analyses reveal that the crystal structures of 1–5 are monoclinic or triclinic system with the space group P 21/c, P−1, P−1, P2(1)/c and P−1, respectively. All P atoms of 1–5 have tetrahedral geometries involving two O-ethyl groups, one Cα atom, and a double bond O atom. The binding interaction of five new α-aminophosphonate N-derivatives (1–5) with calf thymus(CT)-DNA have been investigated by UV–visible and fluorescence emission spectrometry. The apparent binding constant (Kapp) values follows the order: 1 (3.38×105M−1)>2 (3.04×105M−1)>4 (2.52×105M−1)>5 (2.32×105M−1)>3 (2.10×105M−1), suggesting moderate intercalative binding mode between the compounds and DNA. In addition, fluorescence spectrometry of bovine serum albumin (BSA) with the compounds 1–5 showed that the quenching mechanism might be a static quenching procedure. For the compounds 1–5, the number of binding sites were about one for BSA and the binding constants follow the order: 1 (2.72×104M−1)>2 (2.27×104M−1)>4 (2.08×104M−1)>5 (1.79×104M−1)>3 (1.17×104M−1). Moreover, the DNA cleavage abilities of 1 exhibit remarkable changes and the in vitro cytotoxicity of 1 on tumor cells lines (MCF-7, HepG2 and HT29) have been examined by MTT and shown antitumor effect on the tested cells.