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

T. Hertiani, RuAngelie Edrada-Ebel, S. Ortlepp, R.W.M. van Soest, N.J. de Voogd, Victor Wray, Ute Hentschel, Svitlana Kozytska, Werner E.G. Müller, Peter Proksch

Research output: Contribution to journalArticle

96 Citations (Scopus)

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.
LanguageEnglish
Pages1297–1311
Number of pages15
JournalBioorganic and Medicinal Chemistry
Volume18
Issue number3
DOIs
Publication statusPublished - 1 Feb 2010

Fingerprint

Agelas
Biofilms
Porifera
Metabolites
Fouling
Alkaloids
Derivatives
Oximes
Diterpenes
Biological Products
Inhibitory Concentration 50
Larva
Lymphoma
Bearings (structural)
Thoracica
Tyramine
Pyrroles
Spectroscopic analysis
Bioassay
Poisons

Keywords

  • Indonesia
  • marine sponges
  • Agelas linnaei
  • Agelas nakamurai
  • alkaloid derivatives
  • either bromopyrrole
  • diterpene
  • alkaloids
  • brominated pyrroles
  • tyramine analogues
  • taurine analogues
  • diterpene alkaloids
  • Agelas
  • anti-fouling
  • biofilm
  • cytotoxic
  • agelasines
  • mauritamide
  • agelanesins

Cite this

Hertiani, T. ; Edrada-Ebel, RuAngelie ; Ortlepp, S. ; van Soest, R.W.M. ; de Voogd, N.J. ; Wray, Victor ; Hentschel, Ute ; Kozytska, Svitlana ; Müller, Werner E.G. ; Proksch, Peter. / From anti-fouling to biofilm inhibition : new cytotoxic secondary metabolites from two Indonesian Agelas sponges. In: Bioorganic and Medicinal Chemistry . 2010 ; Vol. 18, No. 3. pp. 1297–1311.
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Hertiani, T, Edrada-Ebel, R, Ortlepp, S, van Soest, RWM, de Voogd, NJ, Wray, V, Hentschel, U, Kozytska, S, Müller, WEG & Proksch, P 2010, 'From anti-fouling to biofilm inhibition: new cytotoxic secondary metabolites from two Indonesian Agelas sponges' Bioorganic and Medicinal Chemistry , vol. 18, no. 3, pp. 1297–1311. https://doi.org/10.1016/j.bmc.2009.12.028

From anti-fouling to biofilm inhibition : new cytotoxic secondary metabolites from two Indonesian Agelas sponges. / Hertiani, T.; Edrada-Ebel, RuAngelie; Ortlepp, S.; van Soest, R.W.M.; de Voogd, N.J.; Wray, Victor; Hentschel, Ute; Kozytska, Svitlana; Müller, Werner E.G.; Proksch, Peter.

In: Bioorganic and Medicinal Chemistry , Vol. 18, No. 3, 01.02.2010, p. 1297–1311.

Research output: Contribution to journalArticle

TY - JOUR

T1 - From anti-fouling to biofilm inhibition

T2 - Bioorganic and Medicinal Chemistry

AU - Hertiani, T.

AU - Edrada-Ebel, RuAngelie

AU - Ortlepp, S.

AU - van Soest, R.W.M.

AU - de Voogd, N.J.

AU - Wray, Victor

AU - Hentschel, Ute

AU - Kozytska, Svitlana

AU - Müller, Werner E.G.

AU - Proksch, Peter

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N2 - 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.

AB - 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.

KW - Indonesia

KW - marine sponges

KW - Agelas linnaei

KW - Agelas nakamurai

KW - alkaloid derivatives

KW - either bromopyrrole

KW - diterpene

KW - alkaloids

KW - brominated pyrroles

KW - tyramine analogues

KW - taurine analogues

KW - diterpene alkaloids

KW - Agelas

KW - anti-fouling

KW - biofilm

KW - cytotoxic

KW - agelasines

KW - mauritamide

KW - agelanesins

U2 - 10.1016/j.bmc.2009.12.028

DO - 10.1016/j.bmc.2009.12.028

M3 - Article

VL - 18

SP - 1297

EP - 1311

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

SN - 0968-0896

IS - 3

ER -