Iodination increases the activity of verapamil derivatives in reversing PGP multidrug resistance.

Régis Barattin; Bastien Gerby; Kevin Bourges; Gaëlle Hardy; Jose Olivares; Jean Boutonnat; Christophe Arnoult; Amaury d'Hardemare; Xavier Ronot

Iodination increases the activity of verapamil derivatives in reversing PGP multidrug resistance.

Régis Barattin ¹ Bastien Gerby ² Kevin Bourges ³ Gaëlle Hardy ⁴ Jose Olivares ⁵ Jean Boutonnat ⁶ Christophe Arnoult ³ Amaury d'Hardemare Xavier Ronot ⁷

1 CEMES - Centre d'élaboration de matériaux et d'études structurales

2 CRCT - Centre de Recherche en Cancérologie de Toulouse

3 AGIM - AGeing and IMagery

4 HP2 - Laboratoire de Pharmacologie

5 Bioénergétique fondamentale et appliquée

6 RFMQ

TIMC-IMAG - Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525

7 EPHE

TIMC-IMAG - Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525

Abstract : Iodinated derivatives of verapamil were synthesized and tested as P-glycoprotein (Pgp)-mediated multidrug resistance (MDR) reversal agents. The ability of these compounds to revert MDR was evaluated on daunorubicin-resistant K562 cells, by measuring the intracellular accumulation of rhodamine 123, a fluorescent probe of Pgp transport activity. One of the investigated compounds (16c) was found to be a more potent MDR reversal agent than verapamil and cyclosporin A, used as reference molecules. Further in vitro studies showed that compound 16c restored daunorubicin activity and, when used alone, did not induce cell death, cell cycle perturbation and modification of calcium channel activity in comparison with verapamil.

Document type :

Journal articles

Domain :

Life Sciences [q-bio]

Life Sciences [q-bio] / Cancer

Complete list of metadatas

https://hal.archives-ouvertes.fr/hal-02353716
Contributor : Bastien Gerby <>
Submitted on : Thursday, November 7, 2019 - 2:10:59 PM
Last modification on : Friday, November 8, 2019 - 9:50:39 PM

Iodination increases the activity of verapamil derivatives in reversing PGP multidrug resistance.

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Iodination increases the activity of verapamil derivatives in reversing PGP multidrug resistance.

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