Isolation, structure determination and cytotoxicity studies of tryptophan alkaloids from an Australian marine sponge Hyrtios sp

Shahan Khokhar; Yunjiang Feng; Marc R Campitelli; Merrick G Ekins; John N A Hooper; Karren D Beattie; Martin C Sadowski; Colleen C Nelson; Rohan A Davis

doi:10.1016/j.bmcl.2014.05.104

Isolation, structure determination and cytotoxicity studies of tryptophan alkaloids from an Australian marine sponge Hyrtios sp

Bioorg Med Chem Lett. 2014 Aug 1;24(15):3329-32. doi: 10.1016/j.bmcl.2014.05.104. Epub 2014 Jun 11.

Authors

Shahan Khokhar¹, Yunjiang Feng¹, Marc R Campitelli¹, Merrick G Ekins², John N A Hooper³, Karren D Beattie¹, Martin C Sadowski⁴, Colleen C Nelson⁴, Rohan A Davis⁵

Affiliations

¹ Eskitis Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia.
² Queensland Museum, South Brisbane, QLD 4101, Australia.
³ Eskitis Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia; Queensland Museum, South Brisbane, QLD 4101, Australia.
⁴ Australian Prostate Cancer Research Centre-Queensland Institute of Health and Biomedical Innovation, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, Brisbane, QLD 4102, Australia.
⁵ Eskitis Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia. Electronic address: r.davis@griffith.edu.au.

PMID: 24973030
DOI: 10.1016/j.bmcl.2014.05.104

Abstract

Mass-guided fractionation of the MeOH extract from a specimen of the Australian marine sponge Hyrtios sp. resulted in the isolation of two new tryptophan alkaloids, 6-oxofascaplysin (2), and secofascaplysic acid (3), in addition to the known metabolites fascaplysin (1) and reticulatate (4). The structures of all molecules were determined following NMR and MS data analysis. Structural ambiguities in 2 were addressed through comparison of experimental and DFT-generated theoretical NMR spectral values. Compounds 1-4 were evaluated for their cytotoxicity against a prostate cancer cell line (LNCaP) and were shown to display IC50 values ranging from 0.54 to 44.9 μM.

Keywords: Cytotoxicity; DFT-NMR; Hyrtios; Marine sponge; Tryptophan alkaloid.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alkaloids / chemistry
Alkaloids / isolation & purification
Alkaloids / pharmacology*
Animals
Antineoplastic Agents / chemistry
Antineoplastic Agents / isolation & purification
Antineoplastic Agents / pharmacology*
Australia
Cell Line, Tumor
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Models, Molecular
Molecular Structure
Porifera / chemistry*
Quantum Theory
Structure-Activity Relationship
Tryptophan / chemistry
Tryptophan / isolation & purification
Tryptophan / pharmacology*

Substances

Alkaloids
Antineoplastic Agents
Tryptophan