Improved Dose-Response Relationship of (+)-Discodermolide-Taxol Hybrid Congeners.

ABSTRACT: (+)-Discodermolide is a microtubule-stabilizing agent with potential for the treatment of taxol-refractory malignancies. (+)-Discodermolide congeners containing the C-3'-phenyl side chain of taxol (paclitaxel) were synthesized based on computational docking models predicting this moiety would fill an aromatic pocket of β-tubulin insufficiently occupied by (+)-discodermolide, thereby conferring improved ligand-target interaction. It was recently demonstrated, however, that the C-3'-phenyl side chain occupied a different space, instead extending toward the M-loop of β-tubulin, where it induced a helical conformation, hypothesized to improve lateral contacts between adjacent microtubule protofilaments. This insight led us to evaluate the biological activity of hybrid congeners using a panel o

SUBMITTER: Nadaradjane C 

PROVIDER: S-EPMC6026530 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature