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 DCM - Département de Chimie Moléculaire
2 CaCyS - Laboratoire Cancer, Cycle cellulaire & Sénescence
3 AGIM - AGeing and IMagery
4 HP2 - Laboratoire de Pharmacologie
5 Bioénergétique fondamentale et appliquée
6 RFMQ
7 EPHE - École Pratique des Hautes Études

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.

Domains: Life Sciences [q-bio]; Cancer

Régis Barattin, Bastien Gerby, Kevin Bourges, Gaëlle Hardy, Jose Olivares, et al.. Iodination increases the activity of verapamil derivatives in reversing PGP multidrug resistance.. Anticancer Research, 2010, 30 (7), pp.2553-9. ⟨hal-02353716⟩