Callyaerins A-F and H, new cytotoxic cyclic peptides from the Indonesian marine sponge Callyspongia aerizusa

TY - JOUR

T1 - Callyaerins A-F and H, new cytotoxic cyclic peptides from the Indonesian marine sponge Callyspongia aerizusa

AU - Ibrahim, S.R.M.

AU - Min, C.C.

AU - Teuscher, F.

AU - Ebel, R.

AU - Kakoschke, C.

AU - Lin, W.

AU - Wray, V.

AU - Edrada-Ebel, R.

AU - Proksch, P.

N1 - S. R. M. Ibrahim wishes to thank the Egyptian Government for a scholarship. We are indebted to Professor Dr. W. E. G. Müller (Institute für Physiologische Chemie, Duesbergweg 6, D-55099 Mainz, Germany) for cytotoxicity testing. This project was supported by grants of the BMBF and MOST awarded to Professor Peter Proksch and Professor Wenhan Lin.

PY - 2010/7/15

Y1 - 2010/7/15

N2 - 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 ( H, C 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 ED values of 0.39 and 0.48 µM, respectively. On the other hand, callyaerin A (1) showed strong inhibitory properties towards C. albicans.

AB - 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 ( H, C 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 ED values of 0.39 and 0.48 µM, respectively. On the other hand, callyaerin A (1) showed strong inhibitory properties towards C. albicans.

KW - Callyspongia aerizusa

KW - Callyaerins

KW - Proline-rich cyclic peptides

KW - Cytotoxicity

KW - Antibacterial

KW - Antifungal

UR - http://www.scopus.com/inward/record.url?scp=77955325025&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2010.06.012

DO - 10.1016/j.bmc.2010.06.012

M3 - Article

AN - SCOPUS:77955325025

VL - 18

SP - 4947

EP - 4956

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

SN - 0968-0896

IS - 14

ER -