Boehmeriasin A as new lead compound for the inhibition of topoisomerases and SIRT2
Christodoulou, Michael S × Calogero, Francesco Baumann, Marcus García-Argáez, Aída Nelly Pieraccini, Stefano Sironi, Maurizio Dapiaggi, Federico Bucci, Raffaella Broggini, Gianluigi Gazzola, Silvia Liekens, Sandra Silvani, Alessandra Lahtela-Kakkonen, Maija Martinet, Nadine Nonell-Canals, Alfons Santamaría-Navarro, Eduardo Baxendale, Ian R Dalla Via, Lisa Passarella, Daniele #
European Journal of Medicinal Chemistry vol:92 pages:766-775
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.