Synthesis, anticancer activities, interaction with DNA and mitochondria of manganese complexes.
Two new complexes [(Etdpa)MnCl(2)] and [(Adpa)Mn(Cl)(H(2)O)] (Etdpa = ethyl bis(2-pyridylmethyl)amino-2-propionate; Adpa = bis(2-pyridylmethyl)amino-2-propionic acid) were synthesized and characterized by spectral methods. The crystal structure of [(Etdpa)MnCl(2)] shows that the Mn(II) atom is coordinated by three N atoms (N1, N2, N3), one oxygen atom (O1) of the ligand (Etdpa) and two chloride atoms (Cl1, Cl2), forming a distorted octahedral geometry. The binding interaction between ct-DNA and the synthesized complexes was relatively weak, but they can inhibit the induced swelling of Ca(2+)-loaded mitochondria in a dose-dependent manner. The [(Adpa)Mn(Cl)(H(2)O)] can cause the obvious decrease of mitochondria membrane potential. The MTT (3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenpyltetra-zolium bromide) assay shows that the two Mn(II) complexes are more active against cancer cells. Especially [(Adpa)Mn(Cl)(H(2)O)] can inhibit the proliferation of glioma cells with IC(50) 9.5 μM. Experimental results indicate that the [(Adpa)Mn(Cl)(H(2)O)] could be a new potential antitumor complex to target the mitochondria.
Qiu-Yun
Chen
C
School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013, PR China. chenqy@ujs.edu.cn
Dong-Fang
Zhou
Z
Juan
Huang
H
Wen-Jie
Guo
G
Jing
Gao
G
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000473:pathology; D005260:Female; D005562:Formazans / Q000378:metabolism; D005910:Glioma / Q000188:drug therapy / Q000473:pathology; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008345:Manganese / Q000737:chemistry*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D015394:Molecular Structure; D010100:Oxygen / Q000737:chemistry; D051381:Rats; D012015:Reference Standards; D013778:Tetrazolium Salts / Q000378:metabolism
D000970:Antineoplastic Agents; D056831:Coordination Complexes; D005562:Formazans; D013778:Tetrazolium Salts; C079782:MTT formazan; D008345:Manganese; D004247:DNA; D010100:Oxygen