Bioactive pyrrole alkaloids isolated from the Red Sea: marine sponge Stylissa carteri

Ashraf N. E. Hamed, Roland Schmitz, Anja Bergermann, Frank Totzke, Michael Kubbutat, Werner E. G. Müller, Diaa T.A. Youssef, Mokhtar M. Bishr, Mohamed S. Kamel, RuAngelie Edrada-Ebel, Wim Wätjen, Peter Proksch

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Abstract

Fifteen pyrrole alkaloids were isolated from the Red Sea marine sponge Stylissa carteri and investigated for their biological activities. Four of them were dibrominated [(+) dibromophakelline, Z-3-bromohymenialdisine, (±) ageliferin and 3,4-dibromo-1H-pyrrole-2-carbamide], nine compounds were monobrominated [(-) clathramide C, agelongine, (+) manzacidin A, (-) 3-bromomanzacidin D, Z-spongiacidin D, Z-hymenialdisine, 2-debromostevensine, 2-bromoaldisine and 4-bromo-1H-pyrrole-2-carbamide)] and finally, two compounds were non-brominated derivatives viz., E-debromohymenialdisine and aldisine. The structure elucidations of isolated compounds were based on 1D & 2D NMR spectroscopic and MS studies, as well as by comparison with literature. In-vitro, Z-spongiacidin D exhibited a moderate activity on (ARK5, CDK2-CycA, CDK4/CycD1, VEGF-R2, SAK and PDGFR-beta) protein kinases. Moreover, Z-3-bromohymenialdisine showed nearly similar pattern. Furthermore, Z-hymenialdisine displayed a moderate effect on (ARK5 & VEGF-R2) and (-) clathramide C showed a moderate activity on AURORA-A protein kinases. While, agelongine, (+) manzacidin A, E-debromohymenialdisine and 3,4-dibromo-1H-pyrrole-2-carbamide demonstrated only marginal inhibitory activities. The cytotoxicity study was evaluated in two different cell lines. The most effective secondary metabolites were (+) dibromophakelline and Z-3-bromohymenialdisine on L5178Y. Finally, Z-hymenialdisine, Z-3-bromohymenialdisine and (±) ageliferin exhibited the highest cytotoxic activity on HCT116. No report about inhibition of AURORA-A and B by hymenialdisine/hymenialdisine analogs existed and no reported toxicity of ageliferin existed in literature.

Original languageEnglish
Pages (from-to)199-210
Number of pages12
JournalZeitschrift fur Naturforschung C
Volume73
Issue number5-6
Early online date20 Jan 2018
DOIs
Publication statusPublished - 25 Apr 2018

Keywords

  • Axinella carteri
  • cytotoxicity
  • protein kinase
  • pyrrole alkaloids
  • Stylissa carteri

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    Hamed, A. N. E., Schmitz, R., Bergermann, A., Totzke, F., Kubbutat, M., Müller, W. E. G., Youssef, D. T. A., Bishr, M. M., Kamel, M. S., Edrada-Ebel, R., Wätjen, W., & Proksch, P. (2018). Bioactive pyrrole alkaloids isolated from the Red Sea: marine sponge Stylissa carteri. Zeitschrift fur Naturforschung C, 73(5-6), 199-210. https://doi.org/10.1515/znc-2017-0161