Callyaerins from the Marine Sponge Callyspongia aerizusa: Cyclic Peptides with Antitubercular Activity

• Published in: Journal of natural products (Washington, D.C.) Vol. 78; no. 8; pp. 1910 - 1925
• Main Authors: Daletos, Georgios, Kalscheuer, Rainer, Koliwer-Brandl, Hendrik, Hartmann, Rudolf, de Voogd, Nicole J, Wray, Victor, Lin, Wenhan, Proksch, Peter
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society and American Society of Pharmacognosy 28.08.2015; Amer Chemical Soc
• Subjects: Animals; Antitubercular Agents - chemistry; Antitubercular Agents - isolation & purification; Antitubercular Agents - pharmacology; Callyspongia - chemistry; Callyspongia aerizusa; Chemistry, Medicinal; Drug Screening Assays, Antitumor; Humans; Life Sciences & Biomedicine; Marine; Marine Biology; Molecular Structure; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Nuclear Magnetic Resonance, Biomolecular; Peptides, Cyclic - chemistry; Peptides, Cyclic - isolation & purification; Peptides, Cyclic - pharmacology; Pharmacology & Pharmacy; Plant Sciences; Science & Technology; PROLINE
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.5b00266

Chemical investigation of the Indonesian sponge Callyspongia aerizusa afforded five new cyclic peptides, callyaerins I–M (1–5), along with the known callyaerins A–G (6–12). The structures of the new compounds were unambiguously elucidated on the basis of one- and two-dimensional NMR spectroscopy and mass spectrometry. In addition, the structures of callyaerins D (9), F (11), and G (12), previously available in only small amounts, have been reinvestigated and revised. All compounds were tested in vitro against Mycobacterium tuberculosis, as well as against THP-1 (human acute monocytic leukemia) and MRC-5 (human fetal lung fibroblast) cell lines, in order to assess their general cytotoxicity. Callyaerins A (6) and B (7) showed potent anti-TB activity with MIC90 values of 2 and 5 μM, respectively. Callyaerin C (8) was found to be less active, with an MIC90 value of 40 μM. Callyaerin A (6), which showed the strongest anti-TB activity, was not cytotoxic to THP-1 or MRC-5 cells (IC50 > 10 μM), which highlights the potential of these compounds as promising anti-TB agents.