New retinoid derivatives as back-ups of Adarotene

  • Bioorg Med Chem. 2012 Apr 1;20(7):2405-15. doi: 10.1016/j.bmc.2012.01.042.
Giuseppe Giannini  1 ,  Tiziana Brunetti ,  Gianfranco Battistuzzi ,  Domenico Alloatti ,  Gianandrea Quattrociocchi ,  Maria Grazia Cima ,  Lucio Merlini ,  Sabrina Dallavalle ,  Raffaella Cincinelli ,  Raffaella Nannei ,  Loredana Vesci ,  Federica Bucci ,  Rosanna Foderà ,  Mario Berardino Guglielmi ,  Claudio Pisano ,  Walter Cabri
Affiliations
  • 1. Sigma-Tau Industrie Farmaceutiche Riunite Spa, via Pontina Km 30.400, 00040 Pomezia, Italy. [email protected]
PMID: 22365912 DOI: 10.1016/j.bmc.2012.01.042
Abstract

Adarotene belongs to the so-called class of atypical retinoids. The presence of the phenolic hydroxyl group on Adarotene structure allows a rapid O-glucuronidation as a major mechanism of elimination of the drug, favoring a fast excretion of its glucuronide metabolite in the urines. A series of ether, carbamate and ester derivatives was synthesized. All of them were studied and evaluated for their stability at different pH. The cytotoxic activity in vitro on NCI-H460 non-small cell lung carcinoma and A2780 ovarian tumor cell lines was also tested. A potential back-up of Adarotene has been selected to be evaluated in tumor models.