Probing the biological evaluations of a new designed Pt(II) complex using spectroscopic and theoretical approaches: human hemoglobin as a target.
In recent years, using heavy metal compounds such as platinum as anticancer agent is one of the common ways in chemical therapy. In this study, a new anticancer compound of glycine derivatives of Pt(II) complex (amyl-glycine1, 10-phenanthroline Platinum nitrate) was designed, and the biological effects of this novel compound on the alterations in the function and structure of human hemoglobin (Hb) at different temperatures of 25 and 37°C were assessed by applying various spectroscopic (fluorescence and circular dichroism (CD)) and theoretical methods. Fluorescence data indicated the strong ability of Pt(II) complex to quench the intrinsic fluorescence of Hb. The binding constant, number of binding sites, and thermodynamic parameters at two temperatures were calculated, and the results indicated the major possibility of occurring van der Waals force or hydrogen bond interactions in the Pt(II) complex-Hb interaction. For evaluating the alteration of secondary structure of Hb upon interaction with various concentrations of complex, far-UV CD spectra were used and it was observed that in high dose of complex, significant changes were occurred which is indicative of some side effects in overdosing of this complex. On the other hand, the molecular docking results illustrate that are well in agreement in obtaining data with spectroscopy. Above results suggested that using Pt(II) complex as an anticancer agent, model drug in high-dose usage might cause some disordering in structure and function of Hb as well as improve understanding of the side effects of newly designed metal anticancer drugs undergoing.
a Department of Cell & Molecular Biology, Faculty of Biological Sciences , Kharazmi University , Tehran , Iran.
Omid
O
Abazari
a Department of Cell & Molecular Biology, Faculty of Biological Sciences , Kharazmi University , Tehran , Iran.
Zahra
Z
Shafaei
a Department of Cell & Molecular Biology, Faculty of Biological Sciences , Kharazmi University , Tehran , Iran.
Adeleh
A
Divsalar
b Chemistry and Engineer Chemistry Research Center , Tehran , Iran.
Mahbubeh
M
Eslami-Moghadam
c Department of Medical Nanotechnology, Science and Research Branch , Islamic Azad University , Tehran , Iran.
Behafarid
B
Ghalandari
d Institute of Biochemistry and Biophysics , University of Tehran , Tehran , Iran.|e Center of Excellence in Biothermodynamics , University of Tehran , Tehran , Iran.
Ali Akbar
AA
Saboury
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D031541:Fluorescence Resonance Energy Transfer; D005998:Glycine / Q000737:chemistry* / Q000494:pharmacology; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008962:Models, Theoretical; D008968:Molecular Conformation; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000737:chemistry* / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D013057:Spectrum Analysis / Q000379:methods; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D000970:Antineoplastic Agents; D006454:Hemoglobins; D009944:Organoplatinum Compounds; D005998:Glycine
FRET; Pt(II) complex; hemoglobin; quenching; side effects