Investigation on the interaction of newly designed anticancer Pd(II) complexes with different aliphatic tails and human serum albumin.
The pharmacokinetics and pharmacodynamics of any drug will depend, largely, on the interaction that it has with human serum albumin (HSA), the most abundant plasma protein. The interaction between newly synthesized Pd(II) complexes, 2,2'-bipyridin octyl dithiocarbamato Pd(II) nitrate (Octpd), 2,2'-bipyridin butyl dithiocarbamato Pd(II) nitrate (ButPd), 2,2'-bipyridin ethyl dithiocarbamato Pd(II) nitrate (EtPd), antitumor components, with human serum albumin, a carrier protein, were studied at different temperatures of 27 and 37 degrees C by fluorescence spectroscopy, far UV circular dichroism (CD), and spectrophotometric and differential scanning calorimetry (DSC) techniques. By the analysis of fluorescence intensity, it was observed that Pd(II) complexes have strong abilities to quench the intrinsic fluorescence of HSA through a dynamic quenching procedure. The binding parameters were evaluated by the fluorescence quenching method. The thermodynamic parameters, including DeltaH degrees , DeltaS degrees , and DeltaG degrees , were calculated by the fluorescence quenching method and indicated that hydrophobic forces play a major role in the interaction of Pd(II) complexes with HSA. Far-UV-CD results represented that Pd(II) complexes induced a decrease in content of the alpha helical structure of protein. The binding of newly designed drugs (Pd(II) complexes) on the blood carrier protein of HSA resulted in significant alterations on the structure and conformation of protein via decreasing stability of HSA by decreasing the T(m), a red shift in maximum fluorescence intensity, a decrease in content of the alpha-helical structure, and the increase of the nonpolar or accessible hydrophobic surface of HSA to solvent.
Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran. divsalar@ibb.ut.ac.ir
Adeleh
A
Divsalar
Mohammad Javad
MJ
Bagheri
Ali Akbar
AA
Saboury
Hassan
H
Mansoori-Torshizi
Mojtaba
M
Amani
D000970:Antineoplastic Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002942:Circular Dichroism; D056831:Coordination Complexes / Q000737:chemistry*; D015195:Drug Design; D006801:Humans; D010165:Palladium / Q000737:chemistry*; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013696:Temperature; D013816:Thermodynamics
C547004:2,2'-bipyridin butyl dithiocarbamatopalladium(II); C547005:2,2'-bipyridin ethyl dithiocarbamatopalladium(II); C547003:2,2'-bipyridin octyl dithiocarbamatopalladium(II); D000970:Antineoplastic Agents; D056831:Coordination Complexes; D012709:Serum Albumin; D010165:Palladium