title: Natural products as starting materials for development of second-generation SERCA inhibitors targeted towards prostate cancer cells.
abstract: An analysis of the binding of the 8-O-N-tert-butoxycarbonyl-12-aminododecanoyl derivative of 8-O-debutanoylthapsigargin to the target molecule, the SERCA pump, has revealed the importance of the length and flexibility of the side chain attached to O-8. Based on the analysis a series of analogues to the 2-unsubstituted analogue trilobolide has been constructed and shown to be equipotent with thapsigargin as SERCA inhibitors. Only the 12-Boc-aminododecaonoyl derivative, however, was found to be apoptotic.
authors.affiliation: Department of Medicinal Chemistry, The Danish University of Pharmaceutical Sciences, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Helmer
authors.initials: H
authors.lastname: Søhoel
authors.forename: Anne-Marie Lund
authors.initials: AM
authors.lastname: Jensen
authors.forename: Jesper V
authors.initials: JV
authors.lastname: Møller
authors.forename: Poul
authors.initials: P
authors.lastname: Nissen
authors.forename: Samuel R
authors.initials: SR
authors.lastname: Denmeade
authors.forename: John T
authors.initials: JT
authors.lastname: Isaacs
authors.forename: Carl Erik
authors.initials: CE
authors.lastname: Olsen
authors.forename: S Brøgger
authors.initials: SB
authors.lastname: Christensen
mesh_terms: D000818:Animals; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008958:Models, Molecular; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000473:pathology*; D011817:Rabbits; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
chemical_list: D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases