Potent anticancer prodrugs able to self-assemble after conjugation with squalene moiety. Role of the releasing spacer (Next-SQ-CancerDrugs)
Paola Milla
Aree / Gruppi di ricerca
Partecipanti al progetto
- Stella Barbara (Docente)
- Zonari Daniele (Tecnico/a)
- Milla Paola (Docente)
Descrizione del progetto
Members of other units:
Daniele Passarella (Organic Chem. Dept.UniMi)
Stella Borrelli (Organic Chem. Dept. UniMi)
Giovanna Damia (Mario Negri Inst.)
Graziella Cappelletti (Bioscience Dept, UniMi)
Sponsors:
Local funds (ex_60%) University of Turin, Italy
University of Milan, Italy
Description
This project is based on the synthesis of novel classes of squalene bioconjugates: these compounds contain a squalene tail, that makes them able to self-assemble in water, and a drug unit connected via a easily releasable linker inside cells. The approach allows the release of active drug through reducible linkages as well as spacer/linker activated through enzymatic hydrolysis. Several potent anticancer drugs are screened (taxanes, podophillotoxins, epothilones, colchicine, camptotechin derivatives etc). All the squalenoyl prodrugs can be able to self-assemble and the obtained nanoparticles are fully characterized from a technological point of view. All compounds are evaluated through cell tests and the best candidates are going to be submitted to preclinical evaluation.
References:
- Dosio F et al , 2010. Bioconj. Chem 21, 1349-1361
- Couvreur P. et al 2010 US2010305030
- Passarella D. et al 2010. Eur.J.Med.Chem. 45, 219-226
Keywords:
Anticancer agents, Squalenoyl derivatives, Nanoparticles, Taxanes, Epothilones, Camptotechin