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

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• 作者：Sabrin R.M. Ibrahim ; Cho Cho Min ; Franka Teuscher ; Rainer Ebel ; Christel Kakoschke ; Wenhan Lin ; Victor Wray ; RuAngelie Edrada-Ebel ; Peter Proksch
• 关键词：Callyspongia aerizusa ; Callyaerins ; Proline-rich cyclic peptides ; Cytotoxicity ; Antibacterial ; Antifungal
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2010
• 出版时间：15 July 2010
• 年：2010
• 卷：18
• 期：14
• 页码：4947-4956
• 全文大小：453 K

文摘

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 μM, respectively. On the other hand, callyaerin A (1) showed strong inhibitory properties towards C. albicans.