Abstract
Structural properties of plasmid DNA and model lipid membrane treated with newly synthesized platinum(II) complex cis-[PtCl2{P(CH2CH2COOH)3}2] (cis-DTCEP for short) were studied and compared with effects of anticancer drug cisplatin, cis-[Pt(NH3)2Cl2] (cis-DDP for short). Time Correlated Single Photon Counting Fluorescence Correlation Spectroscopy (TCSPC-FCS) was employed to study interactions between those platinum complexes and DNA. The TCSPC-FCS results suggest that bonding of cis-DTCEP derivative to DNA leads to plasmid strain realignment towards much more compact structure than in the case of cis-DDP. Application of both differential scanning calorimetry and infrared spectroscopy to platinum complexes/DPPC showed that cis-DTCEP slightly increases the phospholipid’s main phase transition temperature resulting in decreased fluidity of the model membrane. The newly investigated compound—similarly to cis-DDP—interacts mainly with the DPPC head group however not only by the means of electrostatic forces: this compound probably enters into hydrophilic region of the lipid bilayer and forms hydrogen bonds with COO groups of glycerol and PO2− group of DPPC.
Highlights
Platinum compounds are very effective in the treatment of ovarian and testicular cancers and in combinations with other antitumor agents are used in the therapy of many carcinomas, e.g., leukemia bladder, breast, small lung, head and neck tumors (Brabec and Kasparkova 2005; Wheate et al 2010; Dasari and Tchounwou 2014; Florea and Busselberg 2011; Alama et al 2009)
One molecule of platinum complex can interact with two heads of DPPC molecules leading to stabilization of DPPC bilayer structure as testified by increasing phase transition temperature
The objective of our work was to investigate molecular interactions between newly obtained platinum(II) with tris(2-carboxyethyl)phosphine complex and DNA and phospholipids as well as to check how they compare against diamminedichloroplatinum (II), a well-known chemotherapeutic drug
Summary
Platinum compounds are very effective in the treatment of ovarian and testicular cancers and in combinations with other antitumor agents are used in the therapy of many carcinomas, e.g., leukemia bladder, breast, small lung, head and neck tumors (Brabec and Kasparkova 2005; Wheate et al 2010; Dasari and Tchounwou 2014; Florea and Busselberg 2011; Alama et al 2009). The aim of synthesis of new analogs of platinum is to increase effectiveness and selectivity against cancer tissues and most of all—decrease the toxicity against health cells. Differences in both activity and toxicity of new complexes of tin stem from the presence of different ligands.
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