Synthesis and characterization of a new macrocyclic copper(II) complex with an N-glycosidic pendant arm: in vitro cytotoxicity and binding studies with calf-thymus DNA.
The new macrocyclic complex 2-amino-2-deoxy-N-[2-(1,3,5,8,11-pentaazacyclotridecan-3-yl)ethyl]-beta-D-glucopyranosylamine copper(II) dichloride (1a) was prepared and thoroughly characterized by various techniques. Molar-conductance measurements showed that 1a (and its Ni analogue 1b) are ionic in nature. On the basis of spectroscopic data, both complexes were assigned a square-planar geometry, and found to be highly stabile and hydrolytically robust in H2O over a wide range of pH, as confirmed by cyclic voltammetry (CV). The Cu(II) complex 1a was found to bind to CT-DNA, with a binding constant Kb of 2.4x10(3) M(-1), as derived by UV/VIS titration, and confirmed by CV, circular dichroism (CD), and viscosity measurements. DNA binding seems to occur mostly via H-bonding. In an in vitro antitumor MTT assay, 1a exhibited significant anticancer activity against the SY5Y and PC-12 cell lines, with an estimated IC50 value in the micromolar range for SYSY, similar to the standard drug 5-fluorouracil.
Mathur
Suvigya
S
Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India.
Tabassum
Sartaj
S
D000818:Animals; D002417:Cattle; D045744:Cell Line, Tumor; D003300:Copper / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D004247:DNA / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006027:Glycosides / Q000138:chemical synthesis* / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D047028:Macrocyclic Compounds / Q000138:chemical synthesis* / Q000378:metabolism / Q000633:toxicity; D016716:PC12 Cells; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats
D006027:Glycosides; D047028:Macrocyclic Compounds; D003300:Copper; D004247:DNA; C427203:calf thymus DNA