Synthesis and biological evaluation of a spongistatin AB-spiroketal analogue.
The synthesis of a simplified analogue of the potent, cytotoxic tubulin-depolymerizing agent spongistatin 1, based on the AB spiroketal framework, is presented. The new structural analogue is an extension of a recently described spongistatin congener reported to disrupt microtubules in breast cancer cells in vitro and to alter the microtubule assembly reaction. Cytotoxicity data on the new structural analogue, as well as the parent congener, are reported. We found no significant cytotoxic or antitubulin activity with either compound.
Smith
Amos B
AB
Department of Chemistry, University of Pennsylvania, PA 19104, USA. smithab@sas.upenn.edu
Corbett
R Michael
RM
Pettit
George R
GR
Chapuis
Jean Charles
JC
Schmidt
Jean M
JM
Hamel
Ernest
E
Jung
M Katherine
MK
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy; D002417:Cattle; D004988:Ethers, Cyclic / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006801:Humans; D007783:Lactones / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D018942:Macrolides; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000095702:Polyether Toxins; D000095662:Polyether Polyketides
D000970:Antineoplastic Agents; D004988:Ethers, Cyclic; D006160:Guanosine Triphosphate; D007783:Lactones; D018942:Macrolides; D013141:Spiro Compounds; D014404:Tubulin; C409088:altohyrtin C; D000095702:Polyether Toxins; C083856:spongistatin 1; C070519:halichondrin B; D000095662:Polyether Polyketides