Synthesis, X-ray crystal structure, DNA/protein binding and cytotoxicity studies of five α-aminophosphonate N-derivatives.
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 Cαatom, 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.
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; State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing 210093, People's Republic of China. Electronic address: wangqm@yctu.edu.cn.
Qingming
Q
Wang
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.
Lei
L
Yang
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.
Hui
H
Ding
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.
Xuanrong
X
Chen
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.
Hua
H
Wang
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. Electronic address: xinhuitang@sina.com.
Xinhui
X
Tang
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D002417:Cattle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D063065:Organophosphonates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D063065:Organophosphonates; D012710:Serum Albumin, Bovine; D004247:DNA; C427203:calf thymus DNA
Bovine Serum Albumin (BSA) binding; Cytotoxicity; DNA binding; α-Aminophosphonate