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Issue 25, 2018
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The cisplatin-based Pt(IV)-diclorofibrato multi-action anticancer prodrug exhibits excellent performances also under hypoxic conditions

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Abstract

Multi-action cisplatin-based mono- (1) and di-clofibric acid (2) Pt(IV) “combo” derivatives were synthesized via both traditional and microwave assisted procedures. The two complexes offered very good performances (IC50 values in a nanomolar range) on a panel of human tumor cell lines, including the highly chemoresistant malignant pleural mesothelioma ones. Moreover, both 1 and 2 bypass the cisplatin resistance. Indeed, cisplatin and clofibric acid, the metabolites of the Pt(IV) → Pt(II) intracellular reduction, proved to act synergistically. The adjuvant action of clofibric acid relies on the activation of peroxisome proliferator-activated receptor α (PPARα) that, in turn, decreases the level of Hypoxia-Inducible Factor-1α. Both compounds induced extensive apoptosis in tumor cells, also via oxidative stress. Finally, 2 exhibited excellent performances also under the hypoxic conditions typical of solid tumors, where cisplatin is less effective.

Graphical abstract: The cisplatin-based Pt(iv)-diclorofibrato multi-action anticancer prodrug exhibits excellent performances also under hypoxic conditions

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Publication details

The article was received on 06 Dec 2017, accepted on 31 May 2018 and first published on 31 May 2018


Article type: Paper
DOI: 10.1039/C7DT04614F
Citation: Dalton Trans., 2018,47, 8268-8282
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    The cisplatin-based Pt(IV)-diclorofibrato multi-action anticancer prodrug exhibits excellent performances also under hypoxic conditions

    E. Gabano, M. Ravera, F. Trivero, S. Tinello, A. Gallina, I. Zanellato, M. B. Gariboldi, E. Monti and D. Osella, Dalton Trans., 2018, 47, 8268
    DOI: 10.1039/C7DT04614F

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