Dataset Information

Platinum(iv) dihydroxido diazido N-(heterocyclic)imine complexes are potently photocytotoxic when irradiated with visible light.

ABSTRACT: A series of trans-di-(N-heterocyclic)imine dihydroxido diazido Pt^IV complexes of the form trans,trans,trans-[Pt(N₃)₂(OH)₂(L₁)(L₂)] where L = pyridine, 2-picoline, 3-picoline, 4-picoline, thiazole and 1-methylimidazole have been synthesised and characterised, and their photochemical and photobiological activity evaluated. Notably, complexes 19 (L₁ = py, L₂ = 3-pic) and 26 (L₁ = L₂ = 4-pic) were potently phototoxic following irradiation with visible light (420 nm), with IC₅₀ values of 4.0 ?M and 2.1 ?M respectively (A2780 cancer cell line), demonstrating greater potency than the previously reported complex 1 (L₁ = L₂ = py; 6.7 ?M); whilst also being minimally toxic in the absence of irradiation. Complexes with mixed N-(heterocyclic)imine ligands 19 and 20 (L₁ = py, L₂ = 4-pic) were particularly photocytotoxic towards cisplatin resistant (A2780cis) cell lines. Complex 18 (L₁ = py, L₂ = 2-pic) was comparatively less photocytotoxic (IC₅₀ value 14.5 ?M) than the other complexes, despite demonstrating the greatest absorbance at the irradiation wavelength and the fastest half-life for loss of the N₃ ? Pt LMCT transition upon irradiation (? _irr = 463 nm) in aqueous solution. Complex 29 (X₁ = X₂ = thiazole) although potently phototoxic (2.4 ?M), was also toxic towards cells in the absence of irradiation.

SUBMITTER: Shaili E

PROVIDER: S-EPMC6844273 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Platinum(iv) dihydroxido diazido N-(heterocyclic)imine complexes are potently photocytotoxic when irradiated with visible light.

Shaili Evyenia E Salassa Luca L Woods Julie A JA Clarkson Guy G Sadler Peter J PJ Farrer Nicola J NJ

Chemical science 20190808 37

A series of trans-di-(N-heterocyclic)imine dihydroxido diazido PtIV complexes of the form trans,trans,trans-[Pt(N3)2(OH)2(L1)(L2)] where L = pyridine, 2-picoline, 3-picoline, 4-picoline, thiazole and 1-methylimidazole have been synthesised and characterised, and their photochemical and photobiological activity evaluated. Notably, complexes 19 (L1 = py, L2 = 3-pic) and ...[more]

PMID: 31803436

Similar Datasets

Project description:Platinum diam(m)ine complexes, such as cisplatin, are successful anticancer drugs, but suffer from problems of resistance and side-effects. Photoactivatable Pt(IV) prodrugs offer the potential of targeted drug release and new mechanisms of action. We report the synthesis, X-ray crystallographic and spectroscopic properties of photoactivatable diazido complexes trans,trans,trans-[Pt(N3)2(OH)2(MA)(Py)] (1; MA=methylamine, Py=pyridine) and trans,trans,trans-[Pt(N3)2(OH)2(MA)(Tz)] (2; Tz=thiazole), and interpret their photophysical properties by TD-DFT modelling. The orientation of the azido groups is highly dependent on H bonding and crystal packing, as shown by polymorphs 1p and 1q. Complexes 1 and 2 are stable in the dark towards hydrolysis and glutathione reduction, but undergo rapid photoreduction with UVA or blue light with minimal amine photodissociation. They are over an order of magnitude more potent towards HaCaT keratinocytes, A2780 ovarian, and OE19 oesophageal carcinoma cells than cisplatin and show particular potency towards cisplatin-resistant human ovarian cancer cells (A2780cis). Analysis of binding to calf-thymus (CT), plasmids, oligonucleotide DNA and individual nucleotides reveals that photoactivated 1 and 2 form both mono- and bifunctional DNA lesions, with preference for G and C, similar to transplatin, but with significantly larger unwinding angles and a higher percentage of interstrand cross-links, with evidence for DNA strand cross-linking further supported by a comet assay. DNA lesions of 1 and 2 on a 50 bp duplex were not recognised by HMGB1 protein, in contrast to cisplatin-type lesions. The photo-induced platination reactions of DNA by 1 and 2 show similarities with the products of the dark reactions of the Pt(II) compounds trans-[PtCl2(MA)(Py)] (5) and trans-[PtCl2(MA)(Tz)] (6). Following photoactivation, complex 2 reacted most rapidly with CT DNA, followed by 1, whereas the dark reactions of 5 and 6 with DNA were comparatively slow. Complexes 1 and 2 can therefore give rapid potent photocytotoxicity and novel DNA lesions in cancer cells, with no activity in the absence of irradiation.

Dataset Information

Platinum(iv) dihydroxido diazido N-(heterocyclic)imine complexes are potently photocytotoxic when irradiated with visible light.

Publications

Platinum(iv) dihydroxido diazido <i>N</i>-(heterocyclic)imine complexes are potently photocytotoxic when irradiated with visible light.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets