Aplyronine A is a potent antitumor macrolide isolated from a Japanese sea hare and depolymerize fibrous actin (polymer) to globular actin (monomer). To investigate the structure-actin depolymerizing activity relationships of aplyronine A, seventeen analogs were synthesized. It was found that the side chain moiety is essential to actin depolymerizing activity whereas the macrolide portion and functional groups were not so important for the activity. To study the binding site of actin toward aplyronine A, the photo-affinity labeling probes were designed and synthesized. These compounds proved to bind to actin efficiently.
To isolate a novel protein phosphatase, three derivatives of 9-antracenecarboxylic acid were designed and synthesized. It was found that the position of the linker was important to inhibit the phosphatase.
Jolkinolide D, a diterpene of plant origin, inhibited tumor invasion into the basement membrane and induced apoptosis in tumor cells. Jolkinolide D has a γ,δ-unsaturated-β-hydroxy-α-methylene lactone unit as the pharmacophore structure, which suggests that jolkinolide D might alkylate biomolecules such as proteins and DNA irreversibly in contrast to popular a-methylenes that alkylate biomolecules reversibly. Jolkinolide D pharmacophore was synthesized and its reactivities toward amino acids, nucleotides, and DNA were investigated. The order of reactivity of jolkinolide D pharmacophore (2) toward nucleophiles is -SH > -NH₂ > nucleic acid bases.