Quinazolinecarboline alkaloid evodiamine as scaffold for targeting topoisomerase I and sirtuins

  • Bioorg Med Chem. 2013 Nov 15;21(22):6920-8. doi: 10.1016/j.bmc.2013.09.030.
Michael S Christodoulou  1 ,  Alessandro Sacchetti ,  Valentina Ronchetti ,  Stefania Caufin ,  Alessandra Silvani ,  Giordano Lesma ,  Gabriele Fontana ,  Fabrizio Minicone ,  Benedetta Riva ,  Micol Ventura ,  Maija Lahtela-Kakkonen ,  Elina Jarho ,  Valentina Zuco ,  Franco Zunino ,  Nadine Martinet ,  Federico Dapiaggi ,  Stefano Pieraccini ,  Maurizio Sironi ,  Lisa Dalla Via ,  Ornella Maria Gia ,  Daniele Passarella
Affiliations
  • 1. Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, 20133 Milano, Italy.
PMID: 24103429 DOI: 10.1016/j.bmc.2013.09.030
Abstract

This paper reports the synthesis of a series of evodiamine derivatives. We assayed the ability to inhibit cell growth on three human tumour cell lines (H460, MCF-7 and HepG2) and we evaluated the capacity to interfere with the catalytic activity of Topoisomerase I both by the relaxation assay and the occurrence of the cleavable complex. Moreover, whose effect on sirtuins 1, 2 and 3 was investigated. Finally, molecular docking analyses were performed in an attempt to rationalize the biological results.

Keywords
Evodiamine; Quinazolinecarboline alkaloids; Sirtuins; Topoisomerase I; enantiomer; ent; epi; epimer.