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

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 twodimensional 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