Aaptamine derivatives with CDK2 inhibitory activities from the South China Sea sponge .

Three new aaptamines () together with two known derivatives () were isolated from the South China Sea sponge . The structures of all compounds were unambiguously elucidated by spectroscopic analyses as well as the comparison with literature data. All the compounds were evaluated for their cytotoxic activities against five human cancer cell lines including H1299, H520, SCG7901, CNE-2 and SW680 cells. As a result, compounds showed moderate cytotoxicities against H1299 and H520 cells with IC values ranging from 12.9 to 20.6 μg/mL. Besides, compounds also showed potent inhibitory activities toward cyclin-dependent kinase-2 (CDK2) with IC values of 14.3, 3.0 and 6.0 μg/mL, respectively. In addition, compounds significantly induced G1 arrests of H1299 cells at low concentrations. Drug affinity responsive target stability (DARTS) experiments were carried out and further demonstrated that compound could effectively bind with CDK2 protein and protect it from the degradation by pronase.