Synthesis,X-ray crystal structure,DNA/protein binding and cytotoxicity studies of five α-aminophosphonate N-derivatives |
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| Institution: | 1. School of Pharmacy, Jiangsu Provincial Key Laboratory of Coastal Wetland Bioresources and Environmental Protection, Yancheng Teachers’ University, Yancheng, Jiangsu 224051, People’s Republic of China;2. State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing 210093, People’s Republic of China;1. Università degli Studi di Firenze, Dipartimento di Chimica, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy;2. Università degli Studi di Firenze, Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche, Polo Scientifico, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy;3. Istituto di Biostrutture e Bioimmagini-CNR, via Mezzocannone 16, 80134 Naples, Italy;1. Dipartimento Scienze del Farmaco e dei Prodotti per la salute, Università degli Studi di Messina, Viale Annunziata, I-98168 Messina, Italy;2. Neurofarba Department, Section of Pharmaceutical and Nutraceutical Sciences, Università degli Studi di Firenze, Sesto Fiorentino (Florence), Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy;3. Institute of Molecular Genetics, ASCR, v.v.i., Vídeňská 1083, Prague 4, 14220, Czech Republic;4. Institute of Organic Chemistry and Biochemistry, ASCR, v.v.i., Flemingovo nám. 2, Prague 6, 16610, Czech Republic;1. University of Florida College of Medicine, Department of Biochemistry and Molecular Biology, Gainesville, FL, USA;2. Dipartimento di Chimica Ugo Schiff, Università degli Studi di Firenze, Via della Lastruccia 3, 50019 Sesto Fiorentino (Firenze), Italy;3. Università degli Studi di Firenze, NEUROFARBA Dept., Sezione di Scienze Farmaceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Florence), Italy;1. School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China;2. Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;1. Institute of Chemistry Timisoara of Romanian Academy, 24 Mihai Viteazul Blv., 300223 Timisoara, Romania;2. “Ilie Murgulescu” Institute of Physical Chemistry, Romanian Academy, Splaiul Independentei 202, 060021 Bucharest, Romania;3. “Petru Poni” Institute of Macromolecular Chemistry, Aleea Grigore Ghica Voda 41 A, 700487 Iasi, Romania |
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| 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 × 105 M−1) > 2 (3.04 × 105 M−1) > 4 (2.52 × 105 M−1) > 5 (2.32 × 105 M−1) > 3 (2.10 × 105 M−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 × 104 M−1) > 2 (2.27 × 104 M−1) > 4 (2.08 × 104 M−1) > 5 (1.79 × 104 M−1) > 3 (1.17 × 104 M−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. |
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| Keywords: | α-Aminophosphonate DNA binding Bovine Serum Albumin (BSA) binding Cytotoxicity |
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