Studies on Lipoxygenase inhibitors from Fungi

Sekhar Rao, K. C. (2003) Studies on Lipoxygenase inhibitors from Fungi. Doctoral thesis, University of Mysore.

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Abstract

<p align="justify">Lipoxygenase (LOX) inhibitors are used as preservatives or antioxidants in food. In medicine, they are used as anti-asthmatic agents, anti-inflammatory, anti-angiogenic, anti-cancer and as anti-atherosclerotic agents. Literature search revealed that inhibitors against LOX from microbial sources were scanty. The present investigation has lead to the isolation of methylbisphenol and asperenone as LOX inhibitors from Aspergillus niger through submerged fermentation. Another LOX inhibitor from the fermented wheat bran of Aspergillus niger-CFR-W-105 has lead to the identification of the novel metabolite as 2-amido-3-hydroxy-6-methoxy-5-methyl-4-(prop-1’-enyl)benzoic acid. Due to the novel inhibitory nature and new structure, the compound was designated as nigerloxin. Since, nigerloxin was produced at reasonably good concentrations in SSF, it was taken for optimization of; physical, nutritional and downstream process parameters for the maximum production of nigerloxin. An analytical method by HPLC was developed to determine the nigerloxin concentration in crude samples. It was found that, at the optimum levels of physico-chemical and down stream process parameters nigerloxin yield was found to be 5.1 mg/g dry wheat bran, which was 2.4 fold higher compared to unoptimized medium. Biochemical studies on nigerloxin revealed that, it inhibits LOX and rat lens aldose reductase with an IC50 values of 79 mM and 69 mM, respectively. Nigerloxin also shows, a free radial scavenging property using 1,1-diphenyl-2-picryl hydrazyl (DPPH) with an ED50 value of 66 mM and invitro antitumor property on EAT cell lines. Studies on the mode of inhibition of nigerloxin against LOX-1 had revealed that it is a reversible and mixed type of inhibitor with a Ki value of 13 mM, finally it was proved that nigerloxin inhibits LOX by the similar mechanism as that of the standard antioxidant NDGA. As an academic interest, the binding of nigerloxin to bovine serum albumin (BSA) was investigated using fluorescence spectroscopy. The fluorescence of BSA was quenched following interaction with nigerloxin and this property was used to determine binding constant (1.006 x 106 M-1) and nigerloxin formed a 1:1 complex with BSA.</p>

Item Type:	Thesis (Doctoral)
Uncontrolled Keywords:	Lipoxygenase Enzyme Inhibitors Fungi Nigerloxin
Subjects:	600 Technology > 05 Chemical engineering > 04 Fermentation Technology 600 Technology > 08 Food technology > 29 Microbiological food > 02 Fungi 500 Natural Sciences and Mathematics > 04 Chemistry and Allied Sciences > 16 Enzyme Chemistry
Divisions:	Fermentation Technology and Bioengineering
Depositing User:	Food Sci. & Technol. Information Services
Date Deposited:	10 Aug 2005
Last Modified:	11 Oct 2018 06:57
URI:	http://ir.cftri.res.in/id/eprint/132

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