14096-57-2Relevant articles and documents
Reactivity and biological properties of a series of cytotoxic PtI 2(amine)2 complexes, either cis or trans configured
Messori, Luigi,Cubo, Leticia,Gabbiani, Chiara,Alvarez-Valdes, Amparo,Michelucci, Elena,Pieraccini, Giuseppe,Rios-Luci, Carla,Leon, Leticia G.,Padron, Jose M.,Navarro-Ranninger, Carmen,Casini, Angela,Quiroga, Adoracion G.
, p. 1717 - 1726 (2012)
Six diiodido-diamine platinum(II) complexes, either cis or trans configured, were prepared, differing only in the nature of the amine ligand (isopropylamine, dimethylamine, or methylamine), and their antiproliferative properties were evaluated against a panel of human tumor cell lines. Both series of complexes manifested pronounced cytotoxic effects, with the trans isomers being, generally, more effective than their cis counterparts. Cell cycle analysis revealed different modes of action for these new Pt(II) complexes with respect to cisplatin. The reactivity of these platinum compounds with a number of biomolecules, including cytochrome c, two sulfur containing modified amino acids, 9-ethylguanine, and a single strand oligonucleotide, was analyzed in depth by mass spectrometry and NMR spectroscopy. Interestingly, significant differences in the reactivity of the investigated compounds toward the various model biomolecules were observed: in particular we observed that trans complexes preferentially release their iodide ligands upon biomolecule binding, while the cis isomers may release the amine ligands with retention of iodides. Such differences in reactivity may have important mechanistic implications and a relevant impact on the respective pharmacological profiles.
Structure-activity relationship studies for three new asymmetric cis-platinum(II) aminoethanol-based complexes
van Rijt, Sabine,van Zutphen, Steven,den Dulk, Hans,Brouwer, Jaap,Reedijk, Jan
, p. 4125 - 4129 (2006)
The design and synthesis of three asymmetrical platinum(II) analogues of cisplatin with substituents on the amine, varying in polarity and steric bulk is presented. Their biological activities, as studied using in vitro cytotoxicity studies in cisplatin sensitive and the corresponding cisplatin resistant cell lines, cellular uptake experiments and in a reaction with model DNA base GMP, are presented. All compounds exhibit promising cytotoxicity in the cisplatin sensitive cell lines albeit lower than cisplatin. On the other hand, the complexes partly overcome cisplatin resistance in the resistant cell lines. A direct correlation between cytotoxicity and cellular uptake was found. Conversely, the rate of reaction of all compounds with the model base GMP was found to be very similar and faster than cisplatin. It was therefore concluded that the difference in activity observed for these complexes is due to differential cellular uptake rather than the reactivity towards the cellular target of platinum complexes, nuclear DNA.
Synthesis, characterization, and antitumor activity of platinum(II) complexes of mixed ammine/amine with bidentate carboxylates
Zhang, Jinchao,Gong, Yuqin,Zheng, Xiaoming
, p. 49 - 57 (2002)
Complexes of the type Pt(II)(CH3NH2)(NH3)[(OC)2 (CH2)n]·0.5H2O [(1)-(3)] (n = 0, 1 and 2) have been synthesized for the first time. At the same time, we also have synthesized thr
A kinetic and mechanistic study of analogous bifunctional dialkylamine platinum(ii) complexes
Olusegun, Moses Ariyo,Reddy, Desigan,Jaganyi, Deogratius
, p. 5138 - 5146 (2020/04/09)
This study was aimed at investigating the comparative substitution behaviour of analogous cis/trans-Pt(ii) complexes with inert dialkylamine ligands. The rate of substitution of the aqua ligands by three nucleophiles, viz. thiourea (TU), 1,3-dimethylthiourea (DMTU) and 1,1,3,3-tetramethylthiourea (TMTU), for the complexes: [cis-Pt(OH2)2(NH3)2](ClO4)2 (cPt), [cis-Pt(OH2)2(NH2CH3)2](ClO4)2 (cPtM), [cis-Pt(OH2)2{NH2CH(CH3)2}2](ClO4)2 (cPtR), [trans-Pt(OH2)2(NH3)2](ClO4)2 (tPt), [trans-Pt(OH2)2(NH2CH3)2](ClO4)2 (tPtM) and [trans-Pt(OH2)2{NH2CH(CH3)2}2](ClO4)2 (tPtR) was investigated under pseudo first-order conditions as a function of concentration and temperature by stopped-flow and UV/visible spectrophotometry. The reactions of the cis-complexes proceed in two concerted steps whereas those of the trans-complexes followed a stepwise mechanism involving rate determining substitution of the first chloride followed by a fast second substitution step, with no intermediates being detected. The pseudo first-order rate constants, kobs obeyed the rate law: kobs = k2[nucleophile]. The trans-complexes were observed to be approximately 103 times more reactive than their corresponding cis-analogues. The electronic and the steric hindrance due to the geometries of the complexes controlled the overall reaction pattern. The order of reactivity of the complexes is tPt > tPtM > tPtR > cPt > cPtM > cPtR. The reactivity of the nucleophiles with the complexes decreases with an increase in steric demand in the order: TU > DMTU > TMTU. The trans-dialkylamine complexes formed distinctly different kinetic products relative to their cis-analogues. 195Pt NMR spectroscopic results confirmed the final kinetic products of each of the cis- and trans-complexes. The negative entropy of activation (ΔS≠) values in all the complexes investigated assert an associative substitution mechanism, with the mechanism being more pronounced in the cis-complexes than in their trans-analogues.
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.
