Abstract
In an ongoing survey for bioactive potential of microorganisms from different biosphere zones of India, a new Chrysosporium lobatum strain BK-3 was isolated from soil sample collected from a biodiversity hotspot, Kaziranga National Park, Assam, India. Bioactivity-guided purification resulted in the isolation of two bioactive compounds whose chemical structures were elucidated by 1H and 13C Nuclear Magnetic Resonance (NMR), 2D-NMR, Fourier Transform Infra-red (FT-IR) and mass spectroscopic techniques, and were identified as α, β-dehydrocurvularin and curvularin. Only curvularin exhibited 80% acetylcholinesterase (AChE) inhibitory activity. Detailed ligand receptor binding interactions were studied for curvularin by molecular docking studies. Further, both curvularin and α, β-dehydrocurvularin had similar level of cytotoxicity against different human tumour cell lines like A549, HeLa, MDA-MB-231 and MCF-7, while α, β-dehydrocurvularin was active against COLO 205 with a IC50 of 7.9 μM, but curvularin was inactive. α, β-Dehydrocurvularin also showed good superoxide anion scavenging activity with an EC50 value of 16.71 μg ml-1. Hence, both these compounds exhibited differences in bioactive profiles and this was probably associated with their minor structural differences. This is a first report on bioactive compounds exhibiting AChE inhibitory, cytotoxicity and antioxidant activities from Chrysosporium lobatum strain BK-3.Electronic supplementary materialThe online version of this article (doi:10.1186/2193-1801-2-122) contains supplementary material, which is available to authorized users.
Highlights
Alzheimer’s disease (AD), the most common neurodegenerative disorder associated with ageing, is accompanied by severe deficiency in choline acetyltransferase activity in the hippocampus and cerebral cortex
Purification, characterization and structure elucidation of bioactive compounds The culture filtrate of strain BK-3 revealed the presence of two major spots in thin-layer chromatography (TLC) with Rf values of 0.5 for compound 1 and 0.3 for compound 2 which were separated in a solvent mixture of methanol:chloroform solvent system
Based on the AChE inhibition and cytotoxicity screen-ing assays, we found that curvularin and α, βdehydrocurvularin have slightly different bioactivity profiles. α, β-Dehydrocurvularin and curvularin and their derivatives were earlier reported to be produced by some fungi such as Aspergillus aureofulgens (Caputo and Viola 1977), Alternaria cinerariae (Arai et al 1989), Curvularia eragrostidis (Bicalho et al 2003), Penicillium sp. (Zhan et al 2004), Nectria galligena (Gutierrez et al 2005) and Eupenicillium sp. (Xie et al 2009)
Summary
Alzheimer’s disease (AD), the most common neurodegenerative disorder associated with ageing, is accompanied by severe deficiency in choline acetyltransferase activity in the hippocampus and cerebral cortex. The comprehensive study of the AChE/inhibitor complexes by X-ray crystallography had indicated that AChE possessed a narrow gorge with two separate ligand binding sites, an acylation site (active site) and a peripheral site which was called peripheral anionic site. Simultaneous binding to the catalytic anionic subsite and the peripherical anionic site is responsible for the enhanced binding of gorge-spanning ligands, such as galanthamine and donepezil (E2020). Recent biochemical studies have shown that the peripherical anionic site is implicated in promoting aggregation of the beta-amyloid (Aβ) peptide responsible for the neurodegenerative process in AD (Greenblatt et al 1999; Tariot 2001; Bar-On et al 2002). The design of inhibitors interacting with the peripherical anionic site is of clear potential interest for treatment of AD (Zeng et al 1999)
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