Dual‐Targeting Dual‐Action Platinum(IV) Platform for Enhanced Anticancer Activity and Reduced Nephrotoxicity

Babak, Maria V.; Liu, Yang; Czarny, Bertrand; Toh, Tan Boon; Hooi, Lissa; Chow, Edward Kai‐Hua; Ang, Wee Han; Gibson, Dan; Pastorin, Giorgia

doi:10.1002/anie.201903112

Cited by 89 publications

(55 citation statements)

References 29 publications

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“…This accidental finding provided a new strategy for the design of novel monoazido-containing Pt(IV) photoactivatable complexes. The conjugation of a bioactive ligand at the axial position of Pt(IV) prodrugs has been extensively studied as a strategy to potentiate the anticancer activity of platinum drugs, and the drugs were known as "dual-action" Pt(IV) prodrugs [51][52][53][54][55][56]. Recently, Kasparkova et al prepared complex 12 (Figure 3) by conjugating a histone deacetylase (HADC) inhibitor, suberoyl-bis-hydroxamic acid (Sub), to the axial position of the diazido Pt(IV) complex [57].…”

Section: The Derivatives Of Diazido Pt(iv) Photoactive Complexesmentioning

confidence: 99%

Photoactivatable Platinum-Based Anticancer Drugs: Mode of Photoactivation and Mechanism of Action

Dai

Wang

2020

Molecules

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Platinum-based anticancer drugs are a class of widely used agents in clinical cancer treatment. However, their efficacy was greatly limited by their severe side effects and the arising drug resistance. The selective activation of inert platinum-based drugs in the tumor site by light irradiation is able to reduce side effects, and the novel mechanism of action of photoactivatable platinum drugs might also conquer the resistance. In this review, the recent advances in the design of photoactivatable platinum-based drugs were summarized. The complexes are classified according to their mode of action, including photoreduction, photo-uncaging, and photodissociation. The rationale of drug design, dark stability, photoactivation process, cytotoxicity, and mechanism of action of typical photoactivatable platinum drugs were reviewed. Finally, the challenges and opportunities for designing more potent photoactivatable platinum drugs were discussed.

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Section: The Derivatives Of Diazido Pt(iv) Photoactive Complexesmentioning

confidence: 99%

Photoactivatable Platinum-Based Anticancer Drugs: Mode of Photoactivation and Mechanism of Action

Dai

Wang

2020

Molecules

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“…For example, triphenylphosphonium (TPP) is widely used as a mitochondrial targeting ligand, which could be taken up by mitochondrial membrane owing to its high lipophilicity and positive charge [12] . Recent studies indicate that TPP‐linked cisplatin (Pt) or doxorubicin (Dox) is able to disrupt mitochondrial DNA (mtDNA) and raise the levels of mitochondrial reactive oxygen species (mtROS), leading to mitochondrial dysfunction [9, 13–15] . However, sufficient anticancer effects could not be achieved by simple delivery of traditional drugs to mitochondria.…”

Section: Introductionmentioning

confidence: 99%

Activatable Mitochondria‐Targeting Organoarsenic Prodrugs for Bioenergetic Cancer Therapy

Luo

Gong

et al. 2020

Angewandte Chemie

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Despite widespread applications for cancer treatment, chemotherapyisrestricted by several limitations,including low targeting specificity,a cquired drug resistance,a nd concomitant adverse side effects.I tr emains challenging to overcome these drawbacks. Herein, we report an ew bioenergetic approach for treating cancer efficiently.Asaproof-ofconcept, we construct activatable mitochondria-targeting organoarsenic prodrugs from organoarsenic compounds and traditional chemotherapeutics.T hese prodrugs could accomplish selective delivery and controlled release of both therapeutic agents to mitochondria, which synergistically promote mitochondrial ROS production and induce mitochondrial DNA damage,finally leading to mitochondria-mediated apoptosis of cancer cells.O ur in vitro and in vivo experiments reveal the excellent anticancer efficacy of these prodrugs,u nderscoring the encouraging outlook of this strategy for effective cancer therapy.

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“…Insight gained by computational investigations inspires new strategies and methods addressing the structure, reactivity and mechanism of various novel drug or prodrug molecules [3,8,18] . More recently, several prodrug molecules based on Pt(IV) centers were designed to present a dual‐threat mechanism where upon reduction cisplatin and additional biologically active ligands are released [5,20–22] …”

Section: Introductionmentioning

confidence: 99%

Cyanide Bridged Platinum‐Iron Complexes as Cisplatin Prodrug Systems: Design and Computational Study

et al. 2020

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The potential role of cyanide‐bridged platinum‐iron complexes as an anti‐cancer Pt(IV) prodrug is studied. We present design principles of a dual‐function prodrug that can upon reduction dissociate and release concurrently six cisplatin units and a ferricyanide anion per prodrug unit. The prodrug molecule is a unique complex of hepta metal centers consisting of a ferricyanide core with six Pt(IV) centers each bonded to the Fe(III) core through a cyano ligand. The functionality of the prodrug is addressed through density functional theory (DFT) calculations.

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Dual‐Targeting Dual‐Action Platinum(IV) Platform for Enhanced Anticancer Activity and Reduced Nephrotoxicity

Abstract: Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Cited by 89 publications

References 29 publications

Photoactivatable Platinum-Based Anticancer Drugs: Mode of Photoactivation and Mechanism of Action

Photoactivatable Platinum-Based Anticancer Drugs: Mode of Photoactivation and Mechanism of Action

Activatable Mitochondria‐Targeting Organoarsenic Prodrugs for Bioenergetic Cancer Therapy

Cyanide Bridged Platinum‐Iron Complexes as Cisplatin Prodrug Systems: Design and Computational Study

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