A new scaffold of topoisomerase I inhibitors: Design, synthesis and biological evaluation

  • Eur J Med Chem. 2016 Nov 29:124:326-339. doi: 10.1016/j.ejmech.2016.08.045.
Alberto Mazza  1 ,  Egle M Beccalli  2 ,  Alessandro Contini  1 ,  Aida Nelly Garcia-Argaez  3 ,  Lisa Dalla Via  4 ,  Maria Luisa Gelmi  1
Affiliations
  • 1. DISFARM, Sezione di Chimica Organica "A. Marchesini", Università di Milano, Via Venezian 21, 20133, Milano, Italy.
  • 2. DISFARM, Sezione di Chimica Organica "A. Marchesini", Università di Milano, Via Venezian 21, 20133, Milano, Italy. Electronic address: [email protected].
  • 3. Fondazione per la Biologia e la Medicina della Rigenerazione T.E.S.-Tissue Engineering and Signalling Onlus, Via F. Marzolo 13, 35131, Padova, Italy.
  • 4. Dipartimento di Scienze del farmaco, Università di Padova, Via F. Marzolo 5, 35131, Padova, Italy.
PMID: 27597409 DOI: 10.1016/j.ejmech.2016.08.045
Abstract

The synthesis of a new hexacyclic system was realized starting from tryptamines and exploiting as a key step a sequential Pd-catalyzed N-arylation/acylation reaction. Having topoisomerases as biological target and the campthotecins class as benchmark, the new scaffold was decorated with substituents having different polarity and tested as Topoisomerase I inhibitors.

Keywords
Amination; Pd-catalysis; Polyheterocyclic systems; Pyrroloacridines; Topoisomerase inhibitors; Triptamine.