31246-69-2Relevant academic research and scientific papers
Human serum albumin binding studies of a new platinum(IV) complex containing the drug pregabalin: experimental and computational methods
Shahabadi, Nahid,Amiri, Sara,Taherpour, Avat (Arman)
, p. 600 - 618 (2019)
A new platinum(IV) complex, [Pt(en)(Cl)2(Pregabalin)2], containing the drug pregabalin was synthesized and characterized by elemental analysis, FT-IR, 1H NMR, mass spectrum, thermogravimetric analysis (TGA), molecular docking and RHF/PM6 method. Also, the interaction of Pt(IV) complex with human serum albumin (HSA) was studied by using UV–vis, fluorometric, circular dichroism (CD) spectroscopies and molecular docking techniques. The results demonstrated that the binding of the complex to HSA caused strong fluorescence quenching of HSA through static quenching mechanism. Hydrogen bonds and van der Waals contacts are the major forces in the stability of protein-Pt(IV) complex and the process of the binding of complex with HSA was enthalpy driven (ΔH = –105.8 kJ·mol?1). The results of CD and UV–vis spectroscopy indicated that the binding of the complex to HSA caused conformational changes in HSA. In addition, the study of molecular docking and RHF/PM6 method confirm the experimental results with respect to the mechanism of binding. (Figure presented.).
Platinum(IV) complexes featuring one or two axial ferrocene bearing ligands - Synthesis, characterization, and cytotoxicity
Banfic?, Jelena,Legin, Anton A.,Jakupec, Michael A.,Galanski, Markus,Keppler, Bernhard K.
, p. 484 - 492 (2014/02/14)
Ferrocenyl compounds show interesting antiproliferative properties. Consequently, ferrocene bearing moieties were prepared and coupled for the first time to anticancer platinum(IV) complexes. The compounds, featuring either one or two axially coordinated ferrocene-containing ligands, were fully characterized by ESI-MS and multinuclear (1H, 13C, 15N, and 195Pt) one- and two-dimensional NMR spectroscopy. Their cytotoxicity was investigated in three human cancer cell lines deriving from ovarian carcinoma (CH1), colon carcinoma (SW480), and non-small-cell lung carcinoma (A549) by means of the colorimetric MTT assay. Promising IC 50 values in the low micromolar range in CH1 and SW480 human cancer cells were found. Copyright
Molecular interaction fields vs. quantum-mechanical-based descriptors in the modelling of lipophilicity of platinum(iv) complexes
Ermondi, Giuseppe,Caron, Giulia,Ravera, Mauro,Gabano, Elisabetta,Bianco, Sabrina,Platts, James A.,Osella, Domenico
supporting information, p. 3482 - 3489 (2013/03/28)
We report QSAR calculations using VolSurf descriptors to model the lipophilicity of 53 Pt(iv) complexes with a diverse range of axial and equatorial ligands. Lipophilicity is measured using an efficient HPLC method. Previous models based on a subset of these data are shown to be inadequate, due to incompatibility of whole molecule descriptors between carboxylato and hydroxido ligands. Instead, the interaction surfaces of complexes with various probes are used as independent descriptors. Partial least squares modelling using three latent variables results in an accurate (R2 = 0.92) and robust model (Q2 = 0.87) of lipophilicity, that moreover highlights the importance of size and hydrophobicity terms and the modest relevance of hydrogen bonding.
Influence of equatorial and axial carboxylato ligands on the kinetic inertness of platinum(IV) complexes in the presence of ascorbate and cysteine and within dld-1 cancer cells
Chen, Catherine K. J.,Zhang, Jenny Z.,Aitken, Jade B.,Hambley, Trevor W.
supporting information, p. 8757 - 8764 (2013/12/04)
The rapid and premature reduction of platinum(IV) complexes in vivo is a significant impediment to these complexes being successfully employed as anticancer prodrugs. This study investigates the influence of the platinum(IV) coordination sphere on the ease of reduction of the platinum center in various biological contexts. In the presence of the biological reductants, ascorbate and cysteine, platinum(IV) complexes with dicarboxylato equatorial ligands were observed to exhibit lower reduction potentials and slower reduction rates than analogous platinum(IV) complexes with dichlorido equatorial ligands. Diaminetetracarboxylatoplatinum(IV) complexes exhibited unusually long half-lives in the presence of excess reductants; however, the complexes exhibited moderate potency in vitro, indicative of rapid reduction within the intracellular environment. By use of XANES spectroscopy, trans-[Pt(OAc) 2(ox)(en)] and trans-[PtCl2(OAc)2(en)] were observed to be reduced at a similar rate within DLD-1 cancer cells. This large variability in kinetic inertness of diaminetetracarboxylatoplatinum(IV) complexes in different biological contexts has significant implications for the design of platinum(IV) prodrugs.
An entry to novel platinum complexes: Carboxylation of dihydroxoplatinum(IV) complexes with succinic anhydride and subsequent derivatization
Reithofer, Michael,Galanski, Markus,Roller, Alexander,Keppler, Bernhard K.
, p. 2612 - 2617 (2007/10/03)
An improved carboxylation method of (OC-6-33)-dichloro-(ethane-1,2-diamine) dihydroxyplatinum(IV) based on succinic anhydride is reported. Reaction of the uncoordinated carboxylic acid with simple amines and alcohols leads to the corresponding amides and esters in the presence of 1,1′- carbonyldiimidazole. The resulting new complexes are characterized by IR, 1H, 13C, 15N, and 195Pt NMR spectroscopy, mass spectrometry, and elemental analysis. This reaction provides an entry to a new class of kinetically inert platinum(IV) complexes. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.
The Influence of the Axial Ligands of a Series of Platinum(IV) Anti-Cancer Complexes on their Reduction to Platinum(II) and Reaction with DNA
Ellis, Leanne T.,Er, Hui Meng,Hambley, Trevor W.
, p. 793 - 806 (2007/10/02)
The electrochemical reduction and DNA binding have been studied for a series of platinum(IV) complexes with Cl(-), OH(-), and carboxylate anions as the axial ligands; , , and , R = CH3, CH2CH3, CH2CH2CH3.Cathodic reduction potentials vary by more than 650 mV with the tetrachloro complex reduced most readily and the dihydroxo least readily.The binding of the complexes correlates with the reduction potentials with the more readily reduced complexes binding more readily to DNA.The influence of the reducing agent glutathione on platinum binding to DNA was found to depend on whether it was added before or after Pt/DNA incubation.The results are consistent with octahedral platinum(IV) binding monofunctionally to DNA, and molecular modelling studies have been used to confirm that this is sterically feasible.The crystal structure of has been determined by X-ray diffraction methods and refined to R = 0.028 (977 F).The crystals are monoclinic, space group C 2/c, a 15.569(6), b 8.104(1), c 13.188(1) Angstroem, β 136.38(2) deg.
