Unique Use of Alkylation for Chemo-Redox Activity by a Pt(IV) Prodrug

Chemistry : a European Journal
Rakesh K Pathak, Shanta Dhar

Abstract

Resistance towards chemotherapeutics displayed by cancer cells is a significant stumbling block against fruitful cisplatin-based therapy. A unique dual-acting chemotherapeutic modality, Platin-B, a prodrug of cisplatin and pipobroman-mimicking alkylating agent, was constructed to circumvent tumor resistance. Platin-B exhibited a superior cytotoxicity profile in cisplatin-resistant cancer cells. Enhanced activity and the ability to overcome cancer-induced resistance of Platin-B was related to adduct formation with intracellular glutathione, followed by the activity of Platin-B on the mitochondria of cells, along with its conventional nuclear activity. Alkylating moieties present on Platin-B enhanced its cellular and subcellular concentration and protected it from early drug sequestration by biological thiols.

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Citations

Nov 25, 2016·Dalton Transactions : an International Journal of Inorganic Chemistry·Koushambi Mitra
Aug 6, 2016·Dalton Transactions : an International Journal of Inorganic Chemistry·Uttara BasuShanta Dhar
Feb 6, 2017·Molecular Cancer Therapeutics·Rakesh K PathakShanta Dhar
Sep 18, 2017·Journal of Inorganic Biochemistry·Awatif Rashed Z AlmotairyAndrea Erxleben

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