Callyaerins from the Marine Sponge <i>Callyspongia aerizusa</i>: Cyclic Peptides with Antitubercular Activity

Chemical investigation of the Indonesian sponge <i>Callyspongia aerizusa</i> afforded five new cyclic peptides, callyaerins I–M (<b>1</b>–<b>5</b>), along with the known callyaerins A–G (<b>6</b>–<b>12</b>). 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 (<b>9</b>), F (<b>11</b>), and G (<b>12</b>), previously available in only small amounts, have been reinvestigated and revised. All compounds were tested in vitro against <i>Mycobacterium tuberculosis</i>, 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 (<b>6</b>) and B (<b>7</b>) showed potent anti-TB activity with MIC₉₀ values of 2 and 5 μM, respectively. Callyaerin C (<b>8</b>) was found to be less active, with an MIC₉₀ value of 40 μM. Callyaerin A (<b>6</b>), 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