Inhibition of beta-site amyloid precursor protein cleaving enzyme 1 and cholinesterases by pterosins via a specific structure-activity relationship with a strong BBB permeability
DC Field | Value | Language |
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dc.contributor.author | Jannat, Susoma | - |
dc.contributor.author | Balupuri, Anand | - |
dc.contributor.author | Ali, Md Yousof | - |
dc.contributor.author | Hong, Seong Su | - |
dc.contributor.author | Choi, Chun Whan | - |
dc.contributor.author | Choi, Yun-Hyeok | - |
dc.contributor.author | Ku, Jin-Mo | - |
dc.contributor.author | Kim, Woo Jung | - |
dc.contributor.author | Leem, Jae Yoon | - |
dc.contributor.author | Kim, Ju Eun | - |
dc.contributor.author | Shrestha, Abinash Chandra | - |
dc.contributor.author | Ham, Ha Neul | - |
dc.contributor.author | Lee, Kee-Ho | - |
dc.contributor.author | Kim, Dong Min | - |
dc.contributor.author | Kang, Nam Sook | - |
dc.contributor.author | Park, Gil Hong | - |
dc.date.accessioned | 2021-09-01T19:06:02Z | - |
dc.date.available | 2021-09-01T19:06:02Z | - |
dc.date.created | 2021-06-19 | - |
dc.date.issued | 2019-02-12 | - |
dc.identifier.issn | 1226-3613 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/67643 | - |
dc.description.abstract | We extracted 15 pterosin derivatives from Pteridium aquilinum that inhibited beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) and cholinesterases involved in the pathogenesis of Alzheimer's disease (AD). (2R)-Pterosin B inhibited BACE1, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with an IC50 of 29.6, 16.2 and 48.1 mu M, respectively. The K-i values and binding energies (kcal/mol) between pterosins and BACE1, AChE, and BChE corresponded to the respective IC50 values. (2R)-Pterosin B was a noncompetitive inhibitor against human BACE1 and BChE as well as a mixed-type inhibitor against AChE, binding to the active sites of the corresponding enzymes. Molecular docking simulation of mixed-type and noncompetitive inhibitors for BACE1, AChE, and BChE indicated novel binding site-directed inhibition of the enzymes by pterosins and the structure-activity relationship. (2R)-Pterosin B exhibited a strong BBB permeability with an effective permeability (P-e) of 60.3x10(-6) cm/s on PAMPA-BBB. (2R)-Pterosin B and (2R,3 R)-pteroside C significantly decreased the secretion of A beta peptides from neuroblastoma cells that overexpressed human beta-amyloid precursor protein at 500 mu M. Conclusively, our study suggested that several pterosins are potential scaffolds for multitarget-directed ligands (MTDLs) for AD therapeutics. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.subject | ALZHEIMERS-DISEASE | - |
dc.subject | NATURAL-PRODUCT | - |
dc.subject | BRACKEN FERN | - |
dc.subject | NITRIC-OXIDE | - |
dc.subject | BRAIN | - |
dc.subject | ACETYLCHOLINESTERASE | - |
dc.subject | ASSAY | - |
dc.subject | PHOSPHORYLATION | - |
dc.subject | EXPRESSION | - |
dc.subject | HYPOTHESIS | - |
dc.title | Inhibition of beta-site amyloid precursor protein cleaving enzyme 1 and cholinesterases by pterosins via a specific structure-activity relationship with a strong BBB permeability | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Park, Gil Hong | - |
dc.identifier.doi | 10.1038/s12276-019-0205-7 | - |
dc.identifier.scopusid | 2-s2.0-85061507998 | - |
dc.identifier.wosid | 000460464200003 | - |
dc.identifier.bibliographicCitation | EXPERIMENTAL AND MOLECULAR MEDICINE, v.51 | - |
dc.relation.isPartOf | EXPERIMENTAL AND MOLECULAR MEDICINE | - |
dc.citation.title | EXPERIMENTAL AND MOLECULAR MEDICINE | - |
dc.citation.volume | 51 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.identifier.kciid | ART002439664 | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.description.journalRegisteredClass | kci | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Research & Experimental Medicine | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Medicine, Research & Experimental | - |
dc.subject.keywordPlus | ALZHEIMERS-DISEASE | - |
dc.subject.keywordPlus | NATURAL-PRODUCT | - |
dc.subject.keywordPlus | BRACKEN FERN | - |
dc.subject.keywordPlus | NITRIC-OXIDE | - |
dc.subject.keywordPlus | BRAIN | - |
dc.subject.keywordPlus | ACETYLCHOLINESTERASE | - |
dc.subject.keywordPlus | ASSAY | - |
dc.subject.keywordPlus | PHOSPHORYLATION | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | HYPOTHESIS | - |
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