Synthesis and cytotoxic activities of chloropyridylimineplatinum(II) and chloropyridyliminecopper(II) surface-functionalized poly(amidoamine) dendrimers.
The preparations of novel platinum and copper metallodendrimers are reported. Surface modified first generation (G0) poly(amidoamine) (PAMAM) dendritic Schiff base, prepared via a condensation reaction was coordinated with platinum chloride and copper chloride yielding [G0-Py(4)-[PtCl(2)](4)] (4D) and [G0-Py(4)-[CuCl(2)](7)] (7E) respectively. These functionalized hyper-branched complexes were characterized by IR spectroscopy and CHN analysis. 4D was further characterized through (1)H and (13)C spectroscopy, while 7E was characterized using matrix-assisted laser desorption ionization time-of-flight (MALDI/TOF) Mass Spectrometer. The cytotoxic effects of the compounds against cells of neoplastic origin (MOLT-4, MCF-7) and cells of benign origin (Chang Liver) were studied. Their cytotoxicities were then compared to their mono-nuclear analogues, [(MeCONHCH(2)CH(2)NCHPy)(PtCl(2))] (1D) and [(MeCONHCH(2)CH(2)NCHPy)(CuCl(2))] (1E). The multi-nuclear complexes showed increased cytotoxic activities as compared to their respective mono-nuclear compounds. Most notably, significant inhibitions were observed for 7E on all cell lines, in which its IC(50) values were 11.1+/-0.6, 10.2+/-1.5 and 8.7+/-0.7microM against MOLT-4, MCF-7 and Chang Liver cells respectively. The multi-nuclear copper-based complexes (7E) are therefore most effective against a cancer cell line (MOLT-4) and a cisplatin-resistant cell line (MCF-7).
Zhao
Xinxin
X
School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore.
Loo
Say Chye Joachim
SC
Lee
Peter Peng-Foo
PP
Tan
Timothy Thatt Yang
TT
Chu
Chit Kay
CK
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000737:chemistry*; D050091:Dendrimers / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007287:Inorganic Chemicals / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008855:Microscopy, Electron, Scanning; D008956:Models, Chemical; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D010984:Platinum / Q000737:chemistry*; D017671:Platinum Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013055:Spectrophotometry, Infrared
D050091:Dendrimers; D007287:Inorganic Chemicals; D017671:Platinum Compounds; C030173:platinum chloride; D010984:Platinum; D003300:Copper