Identification of hCA I, hCA II, AChE and BChE Inhibitory Properties of Some Norcantharimide Derivatives; Molecular Docking, SAR and in silico ADME Studies

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dc.authoridPOLAT KOSE, Leyla/0000-0001-5759-7889
dc.authoridKose, Aytekin/0000-0003-2448-3716
dc.contributor.authorKose, Leyla Polat
dc.contributor.authorKose, Aytekin
dc.date.accessioned2025-03-09T10:49:07Z
dc.date.available2025-03-09T10:49:07Z
dc.date.issued2024
dc.departmentİstanbul Beykent Üniversitesi
dc.description.abstract(3aR,4S,7R,7aS)-2-Alkyl/aryl-3a,4,7,7a-tetrahydro-1H-4,7-epoxyisoindole-1,3(2H)-diones, which are norcantharimide derivatives, were synthesized and their effects on carbonic anhydrase I (hCA I) and II (hCA II), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) inhibitory activity were investigated. For enzyme activity studies, hCA I and II isoenzymes purified from human erythrocytes and the commercially available enzymes AChE and BChE, which are both markers and significantly affect the known symptoms of Alzheimer's disease, were used. The two derivatives exerted efficient inhibition with IC50=4.530 nM (Ki=4.483) and 4.426 nM (Ki=4.696) against hCA I and with IC50=3.825 nM (Ki=3.854) and 3.457 nM (Ki=3.292) against hCA II, respectively. The another two derivatives exerted considerable inhibition with IC50=0.526 nM (Ki=0.224) and 0.575 nM (Ki=0.292) against AChE and with IC50=0.135 nM (Ki=0.057) and IC50=0.180 nM (Ki=0.070) against BChE, respectively. The compounds showed activity at the nanomolar level. These remarkable inhibition results were compared with those of standard inhibitors (acetazolamide for hCA I and II and tacrine for AChE and BChE) of each enzyme, reported, and graphed. In addition, molecular docking studies were carried out by in silico methods and the structure-activity relationship was discussed. The poses of compound 4 c are presented along with the ligand-receptor interaction against all metabolic enzymes. Inhibition activity studies of some norcantharimide derivatives were carried out on hCA I and II, AChE, and BChE enzymes. It was found that the inhibition results had values that were similar to the standards. In addition, molecular docking studies of the N-Ph-norcantharimide derivative were carried out and the structure-activity relationship was elucidated. image
dc.identifier.doi10.1002/slct.202400684
dc.identifier.issn2365-6549
dc.identifier.issue16
dc.identifier.scopus2-s2.0-85191036637
dc.identifier.scopusqualityQ3
dc.identifier.urihttps://doi.org/10.1002/slct.202400684
dc.identifier.urihttps://hdl.handle.net/20.500.12662/4730
dc.identifier.volume9
dc.identifier.wosWOS:001206048200001
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.language.isoen
dc.publisherWiley-V C H Verlag Gmbh
dc.relation.ispartofChemistryselect
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WOS_20250310
dc.subjectTricyclic norcantharimide derivatives
dc.subjectcarbonic anhydrase
dc.subjectacetylcholinesterase
dc.subjectbutyrylcholinesterase
dc.titleIdentification of hCA I, hCA II, AChE and BChE Inhibitory Properties of Some Norcantharimide Derivatives; Molecular Docking, SAR and in silico ADME Studies
dc.typeArticle

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