arenastatin-a and Carcinoma--Lewis-Lung

Two analogues possessing steric hindered substituents on C-15 of arenastatin A (1), a potent cytotoxic spongean depsipeptide, were synthesized and shown to enhance stability in mouse serum. Notably, 15-tert-butylanalogue (6) with higher cytotoxicity exhibited in vivo anti-tumor activity through iv administration different from 1. Additionally, conformation analysis among the two analogues and arenastatin A (1) indicated that the torsion angle from C-14 to C-20 is a conclusive factor for the potent cytotoxicity of 1.

Topics: Animals; Antineoplastic Agents; Carcinoma, Lewis Lung; Cytotoxins; Depsipeptides; Dose-Response Relationship, Drug; Drug Stability; Mice; Molecular Conformation; Porifera; Structure-Activity Relationship; Treatment Outcome