Structure-activity relationship studies on an antitumor marine macrolide using aplyronine a-swinholide A hybrid.

An aplyronine A-swinholide A hybrid, consisting of the macrolactone part of aplyronine A and the side chain part of swinholide A, was designed, synthesized, and biologically evaluated. This hybrid induced protein-protein interactions between two major cytoskeletal proteins actin and tubulin in the same manner as aplyronine A, and exhibited potent cytotoxicity and actin-depolymerizing activity. The importance of the methoxy group in the ,,-trimethylserine ester was clarified by the structure-activity relationship studies of the amino acid moiety by using the hybrid analogs.

Development of a novel inducer of protein-protein interactions based on aplyronine A.

An aplyronine A-swinholide A hybrid, consisting of the macrolactone part of aplyronine A and the side chain part of swinholide A, was designed, synthesized, and evaluated for biological activities. The hybrid retained strong cytotoxicity and actin-depolymerizing activity. In addition, the hybrid induced protein-protein interactions (PPI) between actin and tubulin in the manner of aplyronine A.