Spectroscopic and cytotoxic studies of the novel designed palladium(II) complexes: beta-lactoglobulin and K562 as the targets.
Since palladium complexes have been reported to show fewer side effects relative to other heavy metal anticancer compounds, in this study a new class of four structurally related anticancer Pd(II) complexes including 2,2'-bipyridin-n-butyl dithiocarbamato Pd(II) nitrate (Com-1), 2,2'-bipyridin-n-hexyl dithiocarbamato Pd(II) nitrate (Com-2), 2,2'-bipyridin glycinato Pd(II) nitrate (Com-3) and 2,2'-bipyridin octylglycinato Pd(II) nitrate (Com-4) was designed. The effect of four synthesized ligands on the protein structure and cell proliferation were investigated. Whey carrier proteins beta-lactoglobulin-A and-B (BLG-A and-B) and chronic myelogenous leukemia cell line K562 were the targets. Fluorescence and CD instruments were used to assess effect of the ligands on the protein structure. Growth inhibitory effect of the Pd(II) complexes towards the cancer cells was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Results of fluorescence studies revealed that the complexes had no dithiocarbamate moiety (compounds 3 and 4) could quench the intrinsic fluorescence emission of the proteins at lower concentrations than those had such moiety (compounds 1 and 2). The far-UV-CD studies revealed that the regular secondary structure of BLG-A and -B did not show any noticeable alteration upon interaction with different of Pd(II)-complexes. The results of cell proliferation assay also displayed that Com-1 and Com-2 had more growth inhibitory activity against K562, than Com-3 and Com-4. Our results suggested that addition of dithiocarbamate moiety to structure of Pd(II) complexes probably has important role to improve the antiproliferative properties of the anticancer ligands and fewer effects on the carrier protein structure.
Divsalar
A
A
Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
Saboury
A A
AA
Yousefi
R
R
Moosavi-Movahedi
A A
AA
Mansoori-Torshizi
H
H
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D002417:Cattle; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002942:Circular Dichroism; D005453:Fluorescence; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020014:K562 Cells; D007782:Lactoglobulins / Q000737:chemistry / Q000378:metabolism*; D010165:Palladium / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D017433:Protein Structure, Secondary; D012996:Solutions; D013056:Spectrophotometry, Ultraviolet
D000970:Antineoplastic Agents; D007782:Lactoglobulins; D012996:Solutions; D010165:Palladium