Gemcitabine anti-proliferative activity significantly enhanced upon conjugation with cell-penetrating peptides

Bioorganic & Medicinal Chemistry Letters
Nuno ValePaula Gomes

Abstract

Gemcitabine proven efficiency against a wide range of solid tumors and undergoes deamination to its inactive uridine metabolite, which underlies its low bioavailability, and tumour resistance was also associated with nucleoside transporter alterations. Hence, we have conjugated gemcitabine to cell-penetrating peptides (CPP), in an effort to both mask its aniline moiety and facilitate its delivery into cancer cells. Two CPP-drug conjugates have been synthesized and studied regarding both the time-dependent kinetics of gemcitabine release and their anti-proliferative activity on three different human cancer cell lines. Results obtained reveal a dramatic increase in the anti-proliferative activity of gemcitabine in vitro, upon conjugation with the CPPs. As such, CPP-gemcitabine conjugates emerge as promising leads for cancer therapy.

Citations

Jun 3, 2017·International Journal of Molecular Sciences·Alma D Campos-ParraCarlos Pérez-Plasencia
Sep 14, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Nuno ValeMaria João Gouveia
Feb 13, 2020·Pharmacological Reports : PR·Nuno ValeTiago Fleming Outeiro
Jan 23, 2021·RSC Medicinal Chemistry·Cristiana CorreiaNuno Vale
Jan 16, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Aleksandra Hawryłkiewicz, Natalia Ptaszyńska
Aug 22, 2017·Journal of Controlled Release : Official Journal of the Controlled Release Society·Douglas R VogusSamir Mitragotri

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