Synthesis and biological evaluation of spongistatin/altohyrtin analogues: E-ring dehydration and C46 side-chain truncation.
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.
Paterson
Ian
I
University Chemical Laboratory, Lensfield Road, Cambridge, UK CB2 1EW. ip100@cam.ac.uk
Aceña
Jose L
JL
Bach
Jordi
J
Chen
David Y K
DY
Coster
Mark J
MJ
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
D000970:Antineoplastic Agents; D004988:Ethers, Cyclic; D007783:Lactones; D018942:Macrolides; D017239:Paclitaxel; C083856:spongistatin 1; D000095702:Polyether Toxins