Callyaerins A-F and H, new cytotoxic cyclic peptides from the Indonesian marine sponge Callyspongia aerizusa.
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 microM, respectively. On the other hand, callyaerin A (1) showed strong inhibitory properties towards C. albicans.
Ibrahim
Sabrin R M
SR
Institut für Pharmazeutische Biologie und Biotechnologie, Heinrich-Heine-Universität, Geb. 26.23, Universitätsstrasse 1, D-40225 Düsseldorf, Germany.
Min
Cho Cho
CC
Teuscher
Franka
F
Ebel
Rainer
R
Kakoschke
Christel
C
Lin
Wenhan
W
Wray
Victor
V
Edrada-Ebel
RuAngelie
R
Proksch
Peter
P
D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D001424:Bacterial Infections / Q000188:drug therapy; D047128:Callyspongia / Q000737:chemistry*; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy; D010456:Peptides, Cyclic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology
D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D010456:Peptides, Cyclic