Synthesis and Cytotoxicity Evaluation of C4- and C5-Modified Analogues of the α,β-Unsaturated Lactone of Pironetin.

ABSTRACT: Pironetin is a natural product with potent antiproliferative activity that forms a covalent adduct with α-tubulin via conjugate addition into the natural product's α,β-unsaturated lactone. Although pironetin's α,β-unsaturated lactone is involved in its binding to tubulin, the structure-activity relationship at different positions of the lactone have not been thoroughly evaluated. For a systematic evaluation of the structure-activity relationships at the C4 and C5 positions of the α,β-unsaturated lactone of pironetin, twelve analogues of the natural product were prepared by total synthesis. Modifying the stereochemistry at the C4 and/or C5 positions of the α,β-unsaturated lactone of pironetin resulted in loss of antiproliferative activity in OVCAR5 ovarian cancer cells. While changing the C

SUBMITTER: Huang DS 

PROVIDER: S-EPMC5413833 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature