Total synthesis of a library of designed hybrids of the microtubule-stabilising anticancer agents taxol, discodermolide and dictyostatin.
A hybrid library of the marine natural products dictyostatin and discodermolide, incorporating the taxol or taxotere side chains, were synthesised; preliminary biological evaluation in the PANC-1 cancer cell line revealed significant antiproliferative activity, demonstrating that a macrolide scaffold is an effective surrogate for the baccatin core of taxol.
Paterson
Ian
I
University Chemical Laboratory, Lensfield Road, Cambridge, UK, CB2 1EW. ip100@cam.ac.uk
Naylor
Guy J
GJ
Fujita
Takeshi
T
Guzmán
Esther
E
Wright
Amy E
AE
D000473:Alkanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D002219:Carbamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D045744:Cell Line, Tumor; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism; D017239:Paclitaxel / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D011753:Pyrones / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity
D000473:Alkanes; D000970:Antineoplastic Agents; D002219:Carbamates; D007783:Lactones; D018942:Macrolides; D011753:Pyrones; D050257:Tubulin Modulators; C470814:dictyostatin; C071229:discodermolide; D017239:Paclitaxel