title: Chemoenzymatic synthesis and cytotoxicity of oenanthotoxin and analogues.
abstract: We developed a synthetic scheme for the synthesis of naturally occurring (14R)-oenanthotoxin and several analogs. Key-steps of this synthesis were an efficient homo-coupling of alkynes and a chemoenzymatic resolution of racemic oenanthotoxin using novozyme 435 and vinyl acetate. The compounds were screened for their cytotoxic activity using a photometric sulforhodamine B assays and several human tumor cell lines. Oenanthotoxin and many derivatives thereof were cytotoxic to tumor cell lines as well as to non-malignant mouse fibroblasts. The highest activity was determined for human ovarian cancer cells A2780 with EC50 = 3.8 μM.
authors.affiliation: Martin-Luther-Universität Halle-Wittenberg, Bereich Organische Chemie, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Sommerwerk
authors.affiliation: Martin-Luther-Universität Halle-Wittenberg, Bereich Organische Chemie, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany.
authors.forename: Lucie
authors.initials: L
authors.lastname: Heller
authors.affiliation: Martin-Luther-Universität Halle-Wittenberg, Bereich Organische Chemie, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany.
authors.forename: Bianka
authors.initials: B
authors.lastname: Siewert
authors.affiliation: Martin-Luther-Universität Halle-Wittenberg, Bereich Organische Chemie, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany. Electronic address: rene.csuk@chemie.uni-halle.de.
authors.forename: René
authors.initials: R
authors.lastname: Csuk
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D053281:Enediynes / Q000138:chemical synthesis* / Q000737:chemistry*; D005233:Fatty Alcohols / Q000138:chemical synthesis* / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure
chemical_list: D000970:Antineoplastic Agents; D053281:Enediynes; D005233:Fatty Alcohols; C010719:enanthotoxin
keywords: Antitumor; Oenanthotoxin; SRB assay; Water dropwort