Please use this identifier to cite or link to this item: http://hdl.handle.net/10266/4801
Title: Isolation and Characterization of Xanthine Oxidase Inhibitor(s) from Endophytic Fungi
Authors: Kapoor, Neha
Supervisor: Saxena, Sanjai
Keywords: endophytic fungi, gout, hyperuricemia, xanthine oxidase, inhibitors
Issue Date: 2-Sep-2017
Abstract: The present study was oriented towards the exploration of xanthine oxidase inhibitory potential of fungal endophytes isolated from Indian medicinal plants inhabiting biodiversity hotspots of India. Of 181 endophytic isolates, culture filtrates of 38 isolates were found to exhibit XO inhibitory activity over xanthine-NBT agar plate preliminary assay. Both the quantitative assays indicated ten fungal isolates to be potent producers of xanthine oxidase inhibitory entities. The crude chloroform residue of endophytic fungal isolate, #1 CCSTITD was found to be non-purine in nature and exhibited maximum XO inhibitory activity with IC50 of 0.54 μg/ml which was better than positive control Allopurinol (IC50- 0.93 μg/ml). The potential endophytic fungus was identified using morphological and molecular tools as novel Muscodor species named as Muscodor darjeelingensis. Further, the crude chloroform residue of M. darjeelingensis was fractionated into 18 major fractions using TLC and column chromatography. The fraction 9 was found to exhibit mixed type XO inhibitory potential with Ki value of 17.54 μM which was quite close to the febuxostat (Ki- 14.5 μM). The fraction 9 was pale yellow in color, light sensitive, slightly polar having a melting point >200 ˚C. H1-NMR and C13-NMR spectra of bioactive fraction 9 suggested it to be a long chain unsaturated, hydroxylated terpenoid. Further, IR spectra confirmed the presence of carboxyl group. Mass spectra of bioactive fraction showed parent ion peak at m/z 569 and molecular ion peak at m/z 553. The NMR, IR and ESI-MS spectral data of bioactive fraction 9 was found to be identical to that of dihydroxy-carotenoid Lutein. Hence, the bioactive fraction was proposed to be Lutein. This is the first report of a plant carotenoid being produced by an endophytic fungus which is also a potent XO inhibitor. The present study establishes that endophytic fungi are prolific sources of novel non-purine selective inhibitors of xanthine oxidase (NP-SIXO’s). The isolation of Lutein, as XO inhibitor from endophytic fungi further warrants its further evaluation by in silico docking studies and optimizing using QSAR (Quantitative Structure Activity Relationship) for its development into a pharmacophore in management of long term hyperuricemia and oxidative stress related diseases since lutein is already being used as a nutraceuticals.
URI: http://hdl.handle.net/10266/4801
Appears in Collections:Doctoral Theses@DBT

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