The C29-C34 parts of antitumor macrolide aplyronine A serve as versatile actin-affinity tags.

Anticancer drug development inspired by natural products based on protein-protein interactions (PPI) is a promising strategy. We developed structurally-simplified C29-C34 side-chain analogs of aplyronine A (ApA), an antitumor marine macrolide. Among them, the analog possessing the C23 acyloxy group, the C29 ,-dimethyl-L-alanine ester and the C34 -methyl enamide showed potent actin-depolymerizing activity.

Synthesis and Biological Activities of Aplyronine A Analogues toward the Development of Antitumor Protein-Protein Interaction Inducers between Actin and Tubulin: Conjugation of the C1-C9 Macrolactone Part and the C24-C34 Side Chain.

Aplyronine A (ApA) is an antitumor marine macrolide that induces an protein-protein interaction (PPI) between actin and tubulin. The C1-C9 macrolactone part including the C7 ,,-trimethylserine (TMSer) ester is important for its highly potent activities. To develop new antitumor PPI inducers, four aplyronine analogues were synthesized, which bear the C1-C9 macrolactone part with 0-2 TMSer ester(s) and the C24-C34 actin-binding side chain.