title: Synthesis and biological evaluation of spongistatin/altohyrtin analogues: E-ring dehydration and C46 side-chain truncation.
abstract: Simplified analogues of the potent antimitotic marine macrolide spongistatin 1/altohyrtin A were synthesised and evaluated as growth inhibitory agents against a range of human tumour cell lines, including Taxol-resistant strains, revealing that E-ring dehydration leads to enhanced cytotoxicity at the low picomolar level while truncation of the side-chain at C46 results in a drastic decrease in activity.
authors.affiliation: University Chemical Laboratory, Lensfield Road, Cambridge, UK CB2 1EW. ip100@cam.ac.uk
authors.forename: Ian
authors.initials: I
authors.lastname: Paterson
authors.forename: Jose L
authors.initials: JL
authors.lastname: Aceña
authors.forename: Jordi
authors.initials: J
authors.lastname: Bach
authors.forename: David Y K
authors.initials: DY
authors.lastname: Chen
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Coster
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D004988:Ethers, Cyclic / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007783:Lactones; D018942:Macrolides / Q000138:chemical synthesis / Q000494:pharmacology; D017239:Paclitaxel; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D000095702:Polyether Toxins
chemical_list: D000970:Antineoplastic Agents; D004988:Ethers, Cyclic; D007783:Lactones; D018942:Macrolides; D017239:Paclitaxel; C083856:spongistatin 1; D000095702:Polyether Toxins