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Structure Related Inhibition of Enzyme Systems in Cholinesterases and BACE1 In Vitro by Naturally Occurring Naphthopyrone and Its Glycosides Isolated from Cassia obtusifolia.

ABSTRACT: Cassia obtusifolia Linn. have been used to improve vision, inflammatory diseases, and as hepatoprotective agents and to promote urination from ancient times. In the present study, we investigated the influence of glycosylation of components of C. obtusifolia and structure-activity relationships (SARs) with respect to the inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and ?-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), which are related to Alzheimer's disease (AD). All six C. obtusifolia-derived compounds, rubrofusarin (1), rubrofusarin 6-O-?-d-glucopyranoside (2), rubrofusarin 6-O-?-d-gentiobioside (3), nor-rubrofusarin 6-O-?-d-glucoside (4), isorubrofusarin 10-O-?-d-gentiobioside (5), and rubrofusarin 6-O-?-d-triglucoside (6) showed promising inhibitory activity against AChE/BACE1. Compounds 3 and 4 showed most significant inhibition against AChE and BACE1, respectively. The SARs results emphasized the importance of gentiobiosyl moiety in the rubrofusarin for AChE inhibition, whereas the presence of hydroxyl group at C-8 and the glucosyl moiety at the C-6 position in the nor-rubrofusarin appeared to largely determine BACE1 inhibition. Kinetics and docking studies showed the lowest binding energy and highest affinity for mixed-type inhibitors, 3 and 4. Hydrophobic bonds interactions and the number of hydrogen bonds determined the strength of the protein-inhibitor interaction. These results suggest that C. obtusifolia and its constituents have therapeutic potential, and that the SARs of its active components are further explored with a view towards developing a treatment for AD.

SUBMITTER: Shrestha S

PROVIDER: S-EPMC6017707 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Structure Related Inhibition of Enzyme Systems in Cholinesterases and BACE1 In Vitro by Naturally Occurring Naphthopyrone and Its Glycosides Isolated from Cassia obtusifolia.

Shrestha Srijan S Seong Su Hui SH Paudel Pradeep P Jung Hyun Ah HA Choi Jae Sue JS

Molecules (Basel, Switzerland) 20171228 1

<i>Cassia obtusifolia</i> Linn. have been used to improve vision, inflammatory diseases, and as hepatoprotective agents and to promote urination from ancient times. In the present study, we investigated the influence of glycosylation of components of <i>C. obtusifolia</i> and structure-activity relationships (SARs) with respect to the inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), which are related to ...[more]

PMID: 29283428

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Dataset Information

Structure Related Inhibition of Enzyme Systems in Cholinesterases and BACE1 In Vitro by Naturally Occurring Naphthopyrone and Its Glycosides Isolated from Cassia obtusifolia.

Publications

Structure Related Inhibition of Enzyme Systems in Cholinesterases and BACE1 In Vitro by Naturally Occurring Naphthopyrone and Its Glycosides Isolated from Cassia obtusifolia.

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