title: Boehmeriasin A as new lead compound for the inhibition of topoisomerases and SIRT2.
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.
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, 20133 Milano, Italy.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Christodoulou
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, 20133 Milano, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Calogero
authors.affiliation: Department of Chemistry, University of Durham, South Road, DH1 3LE, Durham, United Kingdom.
authors.forename: Marcus
authors.initials: M
authors.lastname: Baumann
authors.affiliation: Dipartimento di Scienze del Farmaco, Università degli Studi di Padova, Via F. Marzolo 5, 35131 Padova, Italy.
authors.forename: Aída Nelly
authors.initials: AN
authors.lastname: García-Argáez
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, 20133 Milano, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Pieraccini
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, 20133 Milano, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Sironi
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, 20133 Milano, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Dapiaggi
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, 20133 Milano, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Bucci
authors.affiliation: Dipartimento di Scienza e Alta Tecnologia, Università degli Studi dell'Insubria, Via Valleggio 11, 22100 Como, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Broggini
authors.affiliation: Dipartimento di Scienza e Alta Tecnologia, Università degli Studi dell'Insubria, Via Valleggio 11, 22100 Como, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Gazzola
authors.affiliation: Rega Institute for Medical Research, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
authors.forename: Sandra
authors.initials: S
authors.lastname: Liekens
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, 20133 Milano, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Silvani
authors.affiliation: School of Pharmacy, University of Eastern Finland, P. O. Box 1627, 70211 Kuopio, Finland.
authors.forename: Maija
authors.initials: M
authors.lastname: Lahtela-Kakkonen
authors.affiliation: Institute of Chemistry, UMR CNRS 7272, Parc Valrose, Nice 06108, Cedex 2, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Martinet
authors.affiliation: Mind the Byte, S.L., Parc Científic de Barcelona, C/Baldiri Reixac, 4-8, 08028 Barcelona, Spain.
authors.forename: Alfons
authors.initials: A
authors.lastname: Nonell-Canals
authors.affiliation: Mind the Byte, S.L., Parc Científic de Barcelona, C/Baldiri Reixac, 4-8, 08028 Barcelona, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Santamaría-Navarro
authors.affiliation: Department of Chemistry, University of Durham, South Road, DH1 3LE, Durham, United Kingdom.
authors.forename: Ian R
authors.initials: IR
authors.lastname: Baxendale
authors.affiliation: Dipartimento di Scienze del Farmaco, Università degli Studi di Padova, Via F. Marzolo 5, 35131 Padova, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Dalla Via
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, 20133 Milano, Italy. Electronic address: Daniele.Passarella@unimi.it.
authors.forename: Daniele
authors.initials: D
authors.lastname: Passarella
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010616:Phenanthrenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D054837:Quinolizidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D056565:Sirtuin 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D010616:Phenanthrenes; D054837:Quinolizidines; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; C000602799:boehmeriasin A; C474199:SIRT2 protein, human; D056565:Sirtuin 2; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II
keywords: Boehmeriasin A; Sirtuins inhibition; Topoisomerases inhibition; Total synthesis