2. Academic Validation
  3. Boehmeriasin A as new lead compound for the inhibition of topoisomerases and SIRT2

Boehmeriasin A as new lead compound for the inhibition of topoisomerases and SIRT2

  • Eur J Med Chem. 2015 Mar 6:92:766-75. doi: 10.1016/j.ejmech.2015.01.038.
Michael S Christodoulou 1,  Francesco Calogero 1,  Marcus Baumann 2,  Aída Nelly García-Argáez 3,  Stefano Pieraccini 1,  Maurizio Sironi 1,  Federico Dapiaggi 1,  Raffaella Bucci 1,  Gianluigi Broggini 4,  Silvia Gazzola 4,  Sandra Liekens 5,  Alessandra Silvani 1,  Maija Lahtela-Kakkonen 6,  Nadine Martinet 7,  Alfons Nonell-Canals 8,  Eduardo Santamaría-Navarro 8,  Ian R Baxendale 2,  Lisa Dalla Via 3,  Daniele Passarella 9
Affiliations

Affiliations

  • 1 Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, 20133 Milano, Italy.
  • 2 Department of Chemistry, University of Durham, South Road, DH1 3LE, Durham, United Kingdom.
  • 3 Dipartimento di Scienze del Farmaco, Università degli Studi di Padova, Via F. Marzolo 5, 35131 Padova, Italy.
  • 4 Dipartimento di Scienza e Alta Tecnologia, Università degli Studi dell'Insubria, Via Valleggio 11, 22100 Como, Italy.
  • 5 Rega Institute for Medical Research, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
  • 6 School of Pharmacy, University of Eastern Finland, P. O. Box 1627, 70211 Kuopio, Finland.
  • 7 Institute of Chemistry, UMR CNRS 7272, Parc Valrose, Nice 06108, Cedex 2, France.
  • 8 Mind the Byte, S.L., Parc Científic de Barcelona, C/Baldiri Reixac, 4-8, 08028 Barcelona, Spain.
  • 9 Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, 20133 Milano, Italy. Electronic address: Daniele.Passarella@unimi.it.
PMID: 25626146 DOI: 10.1016/j.ejmech.2015.01.038
Abstract

Two synthetic approaches to boehmeriasin A are described. A gram scale racemic preparation is accompanied by an efficient preparation of both the pure enantiomers using the conformationally stable 2-piperidin-2-yl acetaldehyde as starting material. The anti-proliferative activity in three Cancer cell lines (CEM, HeLa and L1210) and two endothelial cell lines (HMEC-1, BAEC) indicates promising activity at the nanomolar range. Topoisomerases and SIRT2 are identified as biological targets and the experimental data has been supported by docking studies.

Keywords

Boehmeriasin A; Sirtuins inhibition; Topoisomerases inhibition; Total synthesis.

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