Inhibitors of Serine Proteases from a Microcystis sp. Bloom Material Collected from Timurim Reservoir, Israel

Two new natural products, micropeptin TR1058 (1) and aeruginosin TR642 (2), were isolated from the hydrophilic extract of bloom material of Microcystis sp. collected from the Timurim water reservoir in Israel. The structures of compounds 1 and 2 were determined using 1D and 2D NMR spectroscopy and HR ESI MS and MS/MS techniques. Micropeptin TR1058 (1) was extremely unstable under the isolation conditions, and several degradation products were identified. NMR analysis of aeruginosin TR642 (2) revealed a mixture of eight isomers, and elucidation of its structure was challenging. Aeruginosin TR642 contains a 4,5-didehydroaraginal subunit that has not been described before. Micropeptin TR1058 (1) inhibited chymotrypsin with an IC(50) of 6.78 µM, and aeruginosin TR642 (2) inhibited trypsin and thrombin with inhibition concentration (IC(50)) values of 3.80 and 0.85 µM, respectively. The structures and biological activities of the new compounds are discussed.