Title:From Basics of Coordination Chemistry to Understanding Cisplatin-analogue Pt
Drugs
Volume: 29
Issue: 22
Author(s): Takashiro Akitsu, Dobrina Tsvetkova*, Yuma Yamamoto, Daisuke Nakane and Irena Kostova
Affiliation:
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University-Sofia, 2 Dunav St., Sofia 1000, Bulgaria
Keywords:
Cisplatin, Pt(II), antitumor drugs, coordination chemistry, physical inorganic chemistry, platinum complexes.
Abstract:
Background: Cisplatin, a platinum complex discovered by Rosenberg in 1969, has long been known
as the first metal-based anticancer agent. Since then, various similar derivatives of cisplatin have been investigated
for pharmacological activity, and the approved complexes have been applied as drugs.
Objectives: The aims of the current study are: 1) to summarize the advantages and dose-limiting effects of the
approved and unapproved chemotherapy platinum cytostatics, 2) to develop new strategies for the development
of platinum anticancer drugs, and 3) to clarify the important factors for the mechanism of action of platinum
complexes.
Methods: A search was conducted in the literature databases, and the obtained information was summarized
and analyzed.
Results: Myelosuppression is the main dose-limiting effect and the reason for the disapproval of platinum complexes,
such as picoplatin, enloplatin, miboplatin, sebriplatin, zeniplatin, spiroplatin, iproplatin, and ormaplatin.
From the basic point of view of inorganic coordination chemistry, such as theoretical calculations, crystal structures
of model complexes, docking structures with nucleic acid molecules, spectroscopy, and biological aspects,
the importance of physicochemical properties of inorganic platinum complexes for their mechanism of action
has been indicated. Spectroscopic methods, such as FTIR, NMR, X-ray crystal structure analysis, and fluorescence
microscopy, are important for the investigation of the conformational changes in the binding of platinum
complexes and DNA.
Conclusion: In the development of platinum complexes, strong anti-cancer drug activity, low toxicity, and resistance
can be obtained by the application of polynuclear platinum agents, complexes with targeted activity,
and nanoparticle formulations. Electronic structure, stereochemical, and thermodynamic properties are essential
for understanding the reaction mechanism of platinum complexes.
