Novel C2–C3′ N-peptide linked macrocyclic taxoids. Part 1: Synthesis and biological activities of docetaxel analogues with a peptide side chain at C3′

A series of novel docetaxel analogues possessing a peptide side chain at the C3′-N position was synthesized. These compounds were designed to mimic a region of the α-tubulin loop that is equivalent to the paclitaxel binding pocket in β-tubulin. Eight new peptidic taxoids were obtained and evaluated as inhibitors of microtubule disassembly, as well as for their cytotoxicity.

Graphical abstractThe synthesis and biological activities of docetaxel analogues possessing a peptide side chain at the C3′-N position are described. The chosen amino acids are part of the α-tubulin loop that is equivalent to the paclitaxel binding pocket in β-tubulin.