2. Academic Validation
  3. A new scaffold of topoisomerase I inhibitors: Design, synthesis and biological evaluation

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

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: egle.beccalli@unimi.it.
  • 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.

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