2. Academic Validation
  3. Quinazolinecarboline alkaloid evodiamine as scaffold for targeting topoisomerase I and sirtuins

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

Affiliation

  • 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.

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