2. Academic Validation
  3. Bioactive pyrrole alkaloids isolated from the Red Sea: marine sponge Stylissa carteri

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

  • Z Naturforsch C J Biosci. 2018 Apr 25;73(5-6):199-210. doi: 10.1515/znc-2017-0161.
Ashraf N E Hamed 1 2,  Roland Schmitz 3,  Anja Bergermann 4,  Frank Totzke 5,  Michael Kubbutat 5,  Werner E G Müller 6,  Diaa T A Youssef 7,  Mokhtar M Bishr 8,  Mohamed S Kamel 1,  RuAngelie Edrada-Ebel 9,  Wim Wätjen 3 4,  Peter Proksch 2
Affiliations

Affiliations

  • 1 Department of Pharmacognosy, Faculty of Pharmacy, Minia University, 61519 Minia, Egypt.
  • 2 Institut für Pharmazeutische Biologie und Biotechnologie, Heinrich-Heine-Universität, Universitätsstrasse 1, Geb. 26.23, 40225 Düsseldorf, Germany.
  • 3 Institut für Toxikologie, 1011007, Heinrich-Heine-Universität, Düsseldorf, Germany.
  • 4 Martin-Luther-Universität Halle-Wittenberg, Faculty III, Institut für Agrar- und Ernährungswissenschaften, Weinbergweg 22, 06120 Halle/Saale, Germany.
  • 5 ProQinase GmbH, Breisacher Str. 117, D-79106 Freiburg, Germany.
  • 6 Institut für Physiologische Chemie, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Düsbergweg 6, 55128 Mainz, Germany.
  • 7 Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
  • 8 Research and Development Department, Mepaco Company, Cairo, 11361, Egypt.
  • 9 Strathclyde Institute of Pharmacy and Biomedical Science, Strathclyde University, The John Arbuthnott Building, 161 Cathedral Street, Glasgow G4 0NR, UK.
PMID: 29353267 DOI: 10.1515/znc-2017-0161
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.

Keywords

Axinella carteri; Stylissa carteri; cytotoxicity; protein kinase; pyrrole alkaloids.

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