Axial functionalisation of photoactive diazido platinum(<scp>iv</scp>) anticancer complexes

Shi, Huayun; Imberti, Cinzia; Clarkson, Guy J.; Sadler, Peter J.

doi:10.1039/d0qi00685h

Cited by 25 publications

(28 citation statements)

References 37 publications

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“…Coumarin itself can act as a light-harvesting antenna and also possesses intrinsic anticancer activity. Interestingly, Pt2 generates blue fluorescence upon irradiation (λ em = 440 nm), attributable to the formation of fluorescent coumarin species upon photoactivation with 465 nm light in aqueous solution . UV–vis spectroscopic studies of the photodecomposition of Pt2 have suggested rapid loss of the azide ligands (within 15 min) upon irradiation with blue light (λ = 420 nm) but high stability under dark conditions.…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, Pt2 generates blue fluorescence upon irradiation (λ em = 440 nm), attributable to the formation of fluorescent coumarin species upon photoactivation with 465 nm light in aqueous solution . UV–vis spectroscopic studies of the photodecomposition of Pt2 have suggested rapid loss of the azide ligands (within 15 min) upon irradiation with blue light (λ = 420 nm) but high stability under dark conditions. Likewise, electron paramagnetic resonance (EPR) studies revealed the formation of • OH and • N 3 radicals upon photoactivation …”

Section: Introductionmentioning

confidence: 99%

“…UV–vis spectroscopic studies of the photodecomposition of Pt2 have suggested rapid loss of the azide ligands (within 15 min) upon irradiation with blue light (λ = 420 nm) but high stability under dark conditions. Likewise, electron paramagnetic resonance (EPR) studies revealed the formation of • OH and • N 3 radicals upon photoactivation …”

Section: Introductionmentioning

confidence: 99%

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Single-Cell Chemistry of Photoactivatable Platinum Anticancer Complexes

et al. 2021

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The Pt(IV) prodrug trans, trans, trans-[Pt(pyridine) 2 (N 3 ) 2 (OH) 2 ] (Pt1) and its coumarin derivative trans, trans, trans-[Pt(pyridine) 2 (N 3 ) 2 (OH)(coumarin-3-carboxylate)] (Pt2) are promising agents for photoactivated chemotherapy. These complexes are inert in the dark but release Pt(II) species and radicals upon visible light irradiation, resulting in photocytotoxicity toward cancer cells. Here, we have used synchrotron techniques to investigate the in-cell behavior of these prodrugs and visualize, for the first time, changes in cellular morphology and Pt localization upon treatment with and without light irradiation. We show that photoactivation of Pt2 induces remarkable cellular damage with extreme alterations to multiple cellular components, including formation of vacuoles, while also significantly increasing the cellular accumulation of Pt species compared to dark conditions. X-ray absorption near-edge structure (XANES) measurements in cells treated with Pt2 indicate only partial reduction of the prodrug upon irradiation, highlighting that phototoxicity in cancer cells may involve not only Pt(II) photoproducts but also photoexcited Pt(IV) species.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Single-Cell Chemistry of Photoactivatable Platinum Anticancer Complexes

et al. 2021

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“…To further investigate the effects of axial functionalization, three mono-functionalized diazido Pt(IV) prodrugs attaching to anticancer agent coumarin-3 carboxylate (cou), PDK inhibitor 4-phenylbutyrate (PhB), or DCA (complexes 83 – 85 , Table 8 ) and three biaxially functionalized prodrugs with further modification with a DCA ligand (complexes 86 – 88 , Table 8 ) were developed ( Shi et al, 2020a ). Notably, mono-functionalized complexes ( 83 – 85 ) with one hydroxide ligand showed higher aqueous solubility and more negative reduction potential, while significantly higher cellular Pt accumulation (ca.…”

Section: Axial Ligandmentioning

confidence: 99%

Ligand Evolution in the Photoactivatable Platinum(IV) Anticancer Prodrugs

et al. 2022

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Photoactivatable Pt(IV) anticancer prodrugs with the structure of [PtIV(N1)(N2)(L1)(L2)(A1)(A2)], where N1 and N2 are non-leaving nitrogen donor ligands, L1 and L2 are leaving ligands, and A1 and A2 are axial ligands, have attracted increasing attention due to their promising photo-cytotoxicity even to cisplatin-resistant cancer cells. These photochemotherapeutic prodrugs have high dark-stability under physiological conditions, while they can be activated by visible light restrained at the disease areas, as a consequence showing higher spatial and temporal controllability and much more safety than conventional chemotherapy. The coordinated ligands to the Pt center have been proved to be pivotal in determining the function and activity of the photoactivatable Pt(IV) prodrugs. In this review, we will focus on the development of the coordinated ligands in such Pt(IV) prodrugs and discuss the effects of diverse ligands on their photochemistry and photoactivity as well as the future evolution directions of the ligands. We hope this review can help to facilitate the design and development of novel photoactivatable Pt(IV) anticancer prodrugs.

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“…Since this modification also has the potential to lead to more facile spontaneous reduction in the dark, evaluation of stability of the complex in the absence of irradiation is important. Modification of the axial ligands of photoactivatable Pt( iv ) diazido complexes to incorporate biotin, 14 guanidinoneomycin, 15 coumarins 16 and naphthalimides, 17 as well as an RGD peptide to target integrin 18 have been reported. However, the synthesis and extensive characterisation of 1 itself has not been reported previously, and we report it here for the first time along with two other complexes.…”

Section: Introductionmentioning

confidence: 99%