Anti-Inflammatory Activity and Structure-Activity Relationships of Brominated Indoles from a Marine MolluscReportar como inadecuado


Anti-Inflammatory Activity and Structure-Activity Relationships of Brominated Indoles from a Marine Mollusc


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1

Marine Ecology Research Centre, School of Environment, Science and Engineering, Southern Cross University, G.P.O. Box 157, Lismore, NSW 2480, Australia

2

Centre for Health Sciences Research, University of Southern Queensland, Toowoomba, QLD 4350, Australia

3

Analytical Research Laboratory, Southern Cross Plant Science, Southern Cross University, G.P.O. Box 157, Lismore, NSW 2480, Australia





*

Author to whom correspondence should be addressed.



Academic Editor: Keith B. Glaser

Abstract Marine molluscs are rich in biologically active natural products that provide new potential sources of anti-inflammatory agents. Here we used bioassay guided fractionation of extracts from the muricid Dicathais orbita to identify brominated indoles with anti-inflammatory activity, based on the inhibition of nitric oxide NO and tumour necrosis factor α TNFα in lipopolysaccharide LPS stimulated RAW264.7 macrophages and prostaglandin E2 PGE2 in calcium ionophore-stimulated 3T3 ccl-92 fibroblasts. Muricid brominated indoles were then compared to a range of synthetic indoles to determine structure-activity relationships. Both hypobranchial gland and egg extracts inhibited the production of NO significantly with IC50 of 30.8 and 40 μg-mL, respectively. The hypobranchial gland extract also inhibited the production of TNFα and PGE2 with IC50 of 43.03 µg-mL and 34.24 µg-mL, respectively. The purified mono-brominated indole and isatin compounds showed significant inhibitory activity against NO, TNFα, and PGE2, and were more active than dimer indoles and non-brominated isatin. The position of the bromine atom on the isatin benzene ring significantly affected the activity, with 5Br > 6Br > 7Br. The mode of action for the active hypobranchial gland extract, 6-bromoindole, and 6-bromoisatin was further tested by the assessment of the translocation of nuclear factor kappa B NFκB in LPS-stimulated RAW264.7 mouse macrophage. The extract 40 µg-mL significantly inhibited the translocation of NFκB in the LPS-stimulated RAW264.7 macrophages by 48.2%, whereas 40 µg-mL of 6-bromoindole and 6-bromoistain caused a 60.7% and 63.7% reduction in NFκB, respectively. These results identify simple brominated indoles as useful anti-inflammatory drug leads and support the development of extracts from the Australian muricid D. orbita, as a new potential natural remedy for the treatment of inflammation. View Full-Text

Keywords: marine natural products; inflammation; NO inhibition; Muricidae; isatin; Tyrian purple marine natural products; inflammation; NO inhibition; Muricidae; isatin; Tyrian purple





Autor: Tarek B. Ahmad 1,2, David Rudd 1, Joshua Smith 1,3, Michael Kotiw 2, Peter Mouatt 3, Lisa M. Seymour 2, Lei Liu 3 and Kirsten Benkendorff 1,*

Fuente: http://mdpi.com/



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