11 research outputs found
Photoactivation of trans diamine platinum complexes in aqueous solution and effect on reactivity towards nucleotides
We show that UVA irradiation (365 nm) of the Pt-IV complex trans,trans,trans-[(PtCl2)-Cl-IV(OH)(2)(dimethylamine) (isopropylamine)] (1), induces reduction to Pt-II photoproducts. For the mixed amine Pt-II complex, trans[(PtCl2)-Cl-II(isopropylamine)(methylamine)] (2), irradiation at 365 nm increases the rate and extent of hydrolysis, triggering the formation of diaqua species. Additionally, irradiation increases the extent of reaction of complex 2 with guanosine-5'-monophosphate and affords mainly the bis-adduct, while reactions with adenosine-5'-monophosphate and cytidine-5'-monophosphate give rise only to mono-nucleotide adducts. Density Functional Theory calculations have been used to obtain insights into the electronic structure of complexes 1 and 2, and their photophysical and photochemical properties. UVA-irradiation can contribute to enhanced cytotoxic effects of diamine platinum drugs with trans geometry
Interactions between Anticancertrans-Platinum Compounds and Proteins: Crystal Structures and ESI-MS Spectra of Two Protein Adducts of trans-(Dimethylamino)(methylamino)dichloridoplatinum(II)
The adducts formed between trans-
(dimethylamino)(methylamino)dichloridoplatinum(II),
[t-PtCl2(dma)(ma)], and two model proteins, i.e., hen egg
white lysozyme and bovine pancreatic ribonuclease, were
independently characterized by X-ray crystallography and
electrospray ionization mass spectrometry. In these
adducts, the PtII center, upon chloride release, coordinates
either to histidine or aspartic acid residues while both
alkylamino ligands remain bound to the metal. Comparison
with the cisplatin derivatives of the same proteins
highlights for [t-PtCl2(dma)(ma)] a kind of biomolecular
metalation remarkably different from that of cisplatin
Interactions between Anticancer <i>trans</i>-Platinum Compounds and Proteins: Crystal Structures and ESI-MS Spectra of Two Protein Adducts of <i>trans</i>-(Dimethylamino)(methylamino)dichloridoplatinum(II)
The adducts formed between <i>trans</i>-(dimethylamino)Â(methylamino)ÂdichloridoplatinumÂ(II),
[t-PtCl<sub>2</sub>(dma)Â(ma)], and two model proteins, i.e., hen egg
white lysozyme and bovine pancreatic ribonuclease, were independently
characterized by X-ray crystallography and electrospray ionization
mass spectrometry. In these adducts, the Pt<sup>II</sup> center, upon
chloride release, coordinates either to histidine or aspartic acid
residues while both alkylamino ligands remain bound to the metal.
Comparison with the cisplatin derivatives of the same proteins highlights
for [t-PtCl<sub>2</sub>(dma)Â(ma)] a kind of biomolecular metalation
remarkably different from that of cisplatin
Reactivity and Biological Properties of a Series of Cytotoxic PtI2(amine)(2) Complexes, Either cis or trans Configured
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
Conjugation of testosterone modifies the interaction of mono-functional cationic platinum(II) complexes with DNA, causing significant alterations to the DNA helix
Previously a range of androgen conjugates with non-conventional platinum(II) complexes have been synthesised with the aim of enhancing cellular delivery, and which have shown increased cytotoxic activity compared with non-steroidal compounds (M. J. Hannon et al., Dalton Trans., 2010, DOI: 10.1039/c0dt00838a). To further study this, the complexes have been assessed for their ability to bind to and alter the structure of DNA. All platinum(II) complexes studied herein bind to model nucleo-bases and DNA, but to our surprise, testosterone-based complexes caused the DNA helix to undergo significant unwinding and bending, whereas non-steroidal control complexes caused minimal structural alterations. These effects are similar to those cisplatin induces on DNA structure despite the fact that these compounds produce a monofunctional lesion. This ability attributed to interactions between the DNA helix and bulky steroidal skeleton of testosterone, coupled with the enhanced cellular delivery induced by the steroid make the steroid approach an exciting way to explore non-conventional platinum drug delivery
Governing the âGolden Age of Infrastructureâ: Assessing Transparency Innovations in Philippine Infrastructure Development
Amidst rising infrastructure investment across the AsiaâPacific, glaring accountability deficits have raised questions about governmentsâ capacity to contain corruption in infrastructure development in the region. Recent developments in the Philippines, however, indicate the presence of challenges related to the ability of digitally enhanced transparency measures to bridge such accountability deficits. This article presents the shifting emphasis in transparency and accountability reforms related to Philippine infrastructure development beginning from the 1990s and assesses transparency innovations under the Duterte administration. While milestone measures such as the establishment of an electronic freedom of information (eFOI) platform have provided convenient access to public information, major hurdles remain in obtaining critical documents concerning infrastructure projects. As borne out in an exercise to request the feasibility studies of 48 flagship infrastructure projects, access to information is still obstructed by factors ranging from technical constraints, uneven service delivery, coordination failures, as well as active legal restrictions against the publicâs right to know