From anti-fouling to biofilm inhibition : new cytotoxic secondary metabolites from two Indonesian Agelas sponges

Hertiani, T. and Edrada-Ebel, RuAngelie and Ortlepp, S. and van Soest, R.W.M. and de Voogd, N.J. and Wray, Victor and Hentschel, Ute and Kozytska, Svitlana and Müller, Werner E.G. and Proksch, Peter (2010) From anti-fouling to biofilm inhibition : new cytotoxic secondary metabolites from two Indonesian Agelas sponges. Bioorganic and Medicinal Chemistry, 18 (3). 1297–1311.

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Abstract

Chemical investigation of Indonesian marine sponges Agelas linnaei and A. nakamurai afforded 24 alkaloid derivatives representing either bromopyrrole or diterpene alkaloids. A. linnaei yielded 16 bromopyrrole alkaloids including 11 new natural products with the latter exhibiting unusual functionalities. The new compounds include the first iodinated tyramine-unit bearing pyrrole alkaloids, agelanesins A-D. These compounds exhibited cytotoxic activity against L5178Y mouse lymphoma cells with IC50 values between 9.25 and 16.76 μM. Further new compounds include taurine acid substituted bromopyrrole alkaloids and a new dibromophakellin derivative. A. nakamurai yielded eight alkaloids among them are three new natural products. The latter include the diterpene alkaloids (−)-agelasine D and its oxime derivative and the new bromopyrrole alkaloid longamide C. (−)-Agelasine D and its oxime derivative exhibited cytotoxicity against L5178Y mouse lymphoma cells (IC50 4.03 and 12.5 μM, respectively). Furthermore, both agelasine derivatives inhibited settling of larvae of Balanus improvisus in an anti-fouling bioassay and proved to be toxic to the larvae. (−)-Agelasine D inhibited the growth of planktonic forms of biofilm forming bacteria S. epidermidis (MIC < 0.0877 μM) but did not inhibit biofilm formation whereas the oxime derivative showed the opposite activity profile and inhibited only biofilm formation but not bacterial growth. The structures of the isolated secondary metabolites were elucidated based on extensive spectroscopic analysis involving one- and two-dimensional NMR as well as mass spectrometry and comparison with literature data.