Abstract
Pironetin is an α-tubulin-binding natural product with potent antiproliferative activity against several cancer cell lines that inhibits cell division by forming a covalent adduct with α-tubulin via a Michael addition into the natural product's α,β-unsaturated lactone. We designed and prepared analogs carrying electron-withdrawing groups at the α-position (C2) of the α,β-unsaturated lactone with the goal to generate potent and selective binding analogs. We prepared derivatives containing halogens, a phenyl, and a methyl group at the C2 position to evaluate the structure-activity relationship at this position. Testing of the analogs in ovarian cancer cell lines demonstrated 100–1000-fold decreased antiproliferative activity.
Original language | English (US) |
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Pages (from-to) | 2789-2793 |
Number of pages | 5 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Volume | 28 |
Issue number | 16 |
DOIs | |
State | Published - Sep 1 2018 |
Keywords
- Cytotoxicity
- Pironetin
- Structure-activity
- Synthesis
- Tubulin