113287-15-3Relevant academic research and scientific papers
Anti-tumor platinum (IV) complexes bearing the anti-inflammatory drug naproxen in the axial position
Tolan, Dina A.,Abdel-Monem, Yasser K.,El-Nagar, Mohamed A.
, (2019)
The role of inflammation in cancer generation is gaining importance in the field of cancer research. The chemo-anti-inflammatory strategy that involves using non-steroidal anti-inflammatory drug compounds as effective anti-tumor agents is being acceded globally. In the present study, seven new Pt (IV) complexes based on cisplatin, carboplatin and oxaliplatin scaffold bearing the anti-inflammatory drug naproxen in the axial position were synthesized and characterized by elemental analysis, ESI-MS, Fourier transform-infrared, 1H- and 195Pt-NMR spectroscopy. The reduction behavior in the presence of ascorbic acid was studied using high-performance liquid chromatography. The cytotoxicity against two human breast cell lines and the anti-inflammatory properties were evaluated. All the complexes are able to promote a comparable activity, with average three- and 13-fold more cytotoxic than cisplatin against MCF7 and MDA-MB-231 cell lines, respectively. The complexes show remarkable anti-inflammatory effects, which indicated their potential in treating cancer associated with inflammation and reducing side-effects of chemotherapy.
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.
Novel tetracarboxylatoplatinum(iv) complexes as carboplatin prodrugs
Varbanov, Hristo P.,Valiahdi, Seied M.,Kowol, Christian R.,Jakupec, Michael A.,Galanski, Markus,Keppler, Bernhard K.
, p. 14404 - 14415 (2013/04/10)
It is widely accepted that platinum(iv) complexes act as prodrugs and have to be activated by reduction to the respective platinum(ii) analogs. Recently it could be shown that introduction of lipophilic carboxylato ligands in the axial position leads to diaminedichloridoplatinum(iv) compounds with exceptionally high cytotoxicity. With the aim of improving the antiproliferative properties of carboplatin, a series of twenty-one novel Pt(iv) complexes, featuring the equatorial ligand sphere of carboplatin as well as lipophilic axial carboxylato ligands, was synthesized. In depth characterization is based on elemental analysis, ESI-MS, ATR-IR, and multinuclear (1H, 13C, 15N, and 195Pt) NMR spectroscopy. Their cytotoxic activity in four cell lines (CH1, SK-OV-3, SW480, and A549), lipophilicity, electrochemistry and additionally the rate of reduction in the presence of ascorbic acid were investigated. In contrast to analogous diaminedicarboxylatodichloridoplatinum(iv) compounds, the cytotoxicity of novel diaminetetracarboxylato counterparts could not substantially be increased by simply enhancing their lipophilic character. It seems that not only the reduction potential, but also the rate of reduction has a tremendous influence on the cytotoxic properties. This has to be taken into account for the development of novel anticancer platinum(iv) agents.
