title: Callyaerins from the Marine Sponge Callyspongia aerizusa: Cyclic Peptides with Antitubercular Activity.
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.
authors.forename: Georgios
authors.initials: G
authors.lastname: Daletos
authors.forename: Rainer
authors.initials: R
authors.lastname: Kalscheuer
authors.forename: Hendrik
authors.initials: H
authors.lastname: Koliwer-Brandl
authors.affiliation: Institute of Complex Systems: Strukturbiochemie, Forschungszentrum Juelich , Wilhelm-Johnen-Straße, 52428 Juelich, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Hartmann
authors.affiliation: Naturalis Biodiversity Center , P.O. Box 9517, 2300 RA Leiden, The Netherlands.
authors.forename: Nicole J
authors.initials: NJ
authors.lastname: de Voogd
authors.affiliation: Helmholtz Centre for Infection Research , Inhoffenstraße 7, 38124 Braunschweig, Germany.
authors.forename: Victor
authors.initials: V
authors.lastname: Wray
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Peking University , Beijing 100191, People's Republic of China.
authors.forename: Wenhan
authors.initials: W
authors.lastname: Lin
authors.forename: Peter
authors.initials: P
authors.lastname: Proksch
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D047128:Callyspongia / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008386:Marine Biology; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010456:Peptides, Cyclic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
chemical_list: D000995:Antitubercular Agents; D010456:Peptides, Cyclic; C000602713:callyaerin A; C000602714:callyaerin B