Bioassay guided fractionation of the EtOAc fraction of the sponge Callyspongia aerizusa yielded seven new
cytotoxic cyclic peptides callyaerins A–F (1–6) and H (8). Their structures were determined using extensive 1D (1H, 13C and DEPT) and 2D (COSY, HMQC, HMBC, TOCSY, and ROESY) NMR and mass spectral (ESI
and HRESI-TOF) data. All compounds were cyclic peptides containing ring systems of 5–9 amino acids
and side chains of 2–5 amino acids in length. An unusual (Z)-2,3-diaminoacrylic acid unit provided the
template for ring closure and afforded the linkage to the peptidic side chain which was always initiated
with a proline moiety. All peptides contained three or more proline residues and the remaining residues
were predominantly hydrophobic residues with all amino acids present in the L form. Callyaerins A–F
(1–6) and H (8) showed biological activity in antibacterial assays and in various cytotoxicity assays
employing different tumour cell-lines (L5178Y, HeLa, and PC12). Callyaerins E (5) and H (8) exhibited
strong activity against the L5178Y cell line with ED50 values of 0.39 and 0.48 lM, respectively. On the
other hand, callyaerin A (1) showed strong inhibitory properties towards C. albicans