SAR Evaluation of Disubstituted Tacrine Analogues as Promising Cholinesterase and Carbonic Anhydrase Inhibitors

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dc.contributor.authorOkten, Salih
dc.contributor.authorEkiz, Makbule
dc.contributor.authorTutar, Ahmet
dc.contributor.authorButun, Burcu
dc.contributor.authorKocyigit, Umit Muhammet
dc.contributor.authorTopcu, Gulacti
dc.contributor.authorGulcin, Ilhami
dc.date.accessioned2020-06-25T18:34:09Z
dc.date.available2020-06-25T18:34:09Z
dc.date.issued2019
dc.departmentKırıkkale Üniversitesi
dc.descriptionTopcu, Gulacti/0000-0002-7946-6545; GULCIN, Ilhami/0000-0001-5993-1668; Okten, Salih/0000-0001-9656-1803
dc.description.abstractBackground: The inhibition of both hydrolysis products of acetylcholine (ACh), Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE), is essential for successful treatment of Alzhemier patients. Objectives: This study was investigated inhibition potentials of recently synthesized disubstituted tacrines derivatives on going our research against AChE, BChE and carbonic anhydrase cyctosolic (hCA I and H) enzymes to explore the Structure activity relationship (SAR). Methods: Inhibitory activities of tested compounds against AChE and BChE were measured by spectrophotometric method, developed by Ellman et al. Furthermore, the disubstituted tacrines were determined as inhibitors of two physiologically relevant CA isoforms, the cytosolic hCA I and H by an esterase assay method. Results: The silyl, thiomethyl and cyano substituted seven membered hydrocycle tacrines (9, 11 and 14) significantly inhibited AChE, compared with starting compound 3 (6,8-dibromo-2,3,4,5-teytrahydro-1H-cyclohepta[1,2-b] quinoline) and reference compounds, galantamine and tacrine, while methoxy substituted seven membered hydrocycle tacrine derivative 10 showed selective inhibition against BChE (IC50 = 563 nM). Interestingly, disubstituted tacrines displayed higher or parallel inhibition to galantamine. Additionally, all these tacrine analogues were recorded to be powerful inhibitor compounds of the cytosolic isoenzyme hCA I with K-i in the range of 43.81-471.67 nM, as well as a moderate selectivity toward hCA II isoenzyme with K-i in the range from 87.14 to 614.68 nM compared with AZA, as standard. Conclusion: The disubstituted seven membered hydrocycle tacrine analogues 9-12 and 14 may have promising anti Alzhemier drug candidate and dibromo six membered hydrocycle 2 and dibromo seven membered hydrocycle 3 derivatives may be novel hCA I and II enzyme inhibitors.en_US
dc.description.sponsorshipSakarya University Research FundSakarya University [2014-0204-008]en_US
dc.description.sponsorshipThis study was supported by grants from the Sakarya University Research Fund (Project number: 2014-0204-008).en_US
dc.identifier.citationÖkten S, Ekiz M, Tutar A, Bütün B, Koçyigit ÜM, Topçu G, et al. SAR Evaluation of Disubstituted Tacrine Analogues as Promising Cholinesterase and Carbonic Anhydrase Inhibitors. Indian J of Pharmaceutical Education and Research. 2019;53(2):268-75.en_US
dc.identifier.doi10.5530/ijper.53.2.35
dc.identifier.endpage275en_US
dc.identifier.issn0019-5464
dc.identifier.issue2en_US
dc.identifier.scopus2-s2.0-85052060661
dc.identifier.scopusqualityQ3
dc.identifier.startpage268en_US
dc.identifier.urihttps://doi.org/10.5530/ijper.53.2.35
dc.identifier.urihttps://hdl.handle.net/20.500.12587/7808
dc.identifier.volume53en_US
dc.identifier.wosWOS:000466869900012
dc.identifier.wosqualityQ4
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.language.isoen
dc.publisherAssoc Pharmaceutical Teachers Indiaen_US
dc.relation.ispartofIndian Journal Of Pharmaceutical Education And Research
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectTacrine derivativesen_US
dc.subjectAcetylcholinesteraseen_US
dc.subjectButyrylcholinesteraseen_US
dc.subjectCarbonic anhydraseen_US
dc.subjectAnticholinegicen_US
dc.subjectSARen_US
dc.titleSAR Evaluation of Disubstituted Tacrine Analogues as Promising Cholinesterase and Carbonic Anhydrase Inhibitorsen_US
dc.typeArticle

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