Syntheses and bioactivities of macrocyclic paclitaxel bis-lactones.
Five macrocyclic paclitaxel bis-lactones and their corresponding open chain taxoids were synthesized as models of the tubulin-binding conformation of paclitaxel. Macrocyclic lactones with a 19-21-membered ring underwent isomerization to form smaller rings. The lactones were evaluated for cytotoxicity and tubulin-polymerization ability. All five macrocyclic paclitaxel lactones were active, but less so than paclitaxel, while the rearranged macrocyclic lactones and the corresponding open-chain taxoids were much less active or inactive.
Liu
Changhui
C
Department of Chemistry, M/C 0212, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
Schilling
Jennifer K
JK
Ravindra
Rudravajhala
R
Bane
Susan
S
Kingston
David G I
DG
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001952:Bridged-Ring Compounds; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D007536:Isomerism; D007783:Lactones / Q000138:chemical synthesis / Q000494:pharmacology; D047028:Macrocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008968:Molecular Conformation; D017239:Paclitaxel / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D043823:Taxoids / Q000138:chemical synthesis / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators
D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D007783:Lactones; D047028:Macrocyclic Compounds; D043823:Taxoids; D014404:Tubulin; D050257:Tubulin Modulators; D017239:Paclitaxel