Activation of phenyl 4-(2-Oxo-3-alkylimidazolidin-1-yl)benzenesulfonates prodrugs by CYP1A1 as new antimitotics targeting breast cancer cells
Fiche du document
- 20.500.11794/34622
- 0022-2623
- doi: 10.1021/acs.jmedchem.7b00343
- 28535350
http://purl.org/coar/access_right/c_abf2
Sujets proches
BreastsCiter ce document
Sébastien Fortin et al., « Activation of phenyl 4-(2-Oxo-3-alkylimidazolidin-1-yl)benzenesulfonates prodrugs by CYP1A1 as new antimitotics targeting breast cancer cells », CorpusUL, l'archive ouverte de l'université Laval, ID : 10.1021/acs.jmedchem.7b00343
Métriques
Partage / Export
Résumé
Prodrug-mediated utilization of the cytochrome P450 (CYP) 1A1 to obtain the selective release of potent anticancer products within cancer tissues is a promising approach in chemotherapy. We herein report the rationale, preparation, biological evaluation and mechanism of action of phenyl 4-(2-oxo-3-alkylimidazolidin-1-yl)benzenesulfonates (PAIB-SOs), that are antimicrotubule prodrugs activated by CYP1A1. Although PAIBSOs are inert in most cells tested, they are highly cytocidal towards several human breast cancer cells, including hormone-independent and chemoresistant types. PAIB-SOs are Ndealkylated into cytotoxic phenyl 4-(2-oxo-3-imidazolidin-1-yl)benzenesulfonates (PIBSOs) in CYP1A1-positive cancer cells, both in vitro and in vivo. In conclusion, PAIBSOs are novel chemotherapeutic prodrugs with no equivalent among current antineoplastics, and whose selective action toward breast cancer is tailored to the characteristic pattern of CYP1A1 expression observed in a large percentage of human breast tumors.
