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

  • J Nat Prod. 2015 Aug 28;78(8):1910-25. doi: 10.1021/acs.jnatprod.5b00266.
Georgios Daletos ,  Rainer Kalscheuer ,  Hendrik Koliwer-Brandl ,  Rudolf Hartmann  1 ,  Nicole J de Voogd  2 ,  Victor Wray  3 ,  Wenhan Lin  4 ,  Peter Proksch
Affiliations
  • 1. Institute of Complex Systems: Strukturbiochemie, Forschungszentrum Juelich , Wilhelm-Johnen-Straße, 52428 Juelich, Germany.
  • 2. Naturalis Biodiversity Center , P.O. Box 9517, 2300 RA Leiden, The Netherlands.
  • 3. Helmholtz Centre for Infection Research , Inhoffenstraße 7, 38124 Braunschweig, Germany.
  • 4. State Key Laboratory of Natural and Biomimetic Drugs, Peking University , Beijing 100191, People's Republic of China.
PMID: 26213786 DOI: 10.1021/acs.jnatprod.5b00266
Abstract

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.