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

Simple item page
dc.contributor.authorÖKTEN, S
dc.contributor.authorEKIZ, M
dc.contributor.authorTUTAR, A
dc.contributor.authorBÜTÜN, BURCU
dc.contributor.authorGülçin, İlhami
dc.contributor.authorTOPÇU, GÜLAÇTI
dc.contributor.institutionauthorBÜTÜN, BURCU
dc.contributor.institutionauthorTOPÇU, GÜLAÇTI
dc.date.accessioned2019-10-05T13:45:34Z
dc.date.available2019-10-05T13:45:34Z
dc.date.issued2019-04-01
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.
dc.identifier10.1097/prs.0000000000001927
dc.identifier.citationÖKTEN S., EKIZ M., TUTAR A., BÜTÜN B., Koçyiğit Ü. M. , TOPÇU G., Gülçin İ., -SAR Evaluation of Disubstituted Tacrine Analogues as Promising Cholinesterase and Carbonic Anhydrase Inhibitors-, INDIAN JOURNAL OF PHARMACEUTICAL EDUCATION AND RESEARCH, cilt.13, ss.23-30, 2019
dc.identifier.urihttps://hdl.handle.net/20.500.12645/2919
dc.language.isoen
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleSAR Evaluation of Disubstituted Tacrine Analogues as Promising Cholinesterase and Carbonic Anhydrase Inhibitors
dc.typeArticle
dspace.entity.typePublication
local.article.journalnamePLASTIC AND RECONSTRUCTIVE SURGERY
local.avesis.id46f8a420-15c2-4dfa-9cad-292feec68d21
local.avesis.response2789
local.publication.goal08 - İnsana Yakışır İş ve Ekonomik Büyüme
relation.isAuthorOfPublicationead52e9e-d5ef-4a56-8642-bdeed96e65c2
relation.isAuthorOfPublication3c94748e-c303-4294-ad67-c5a0739628e5
relation.isAuthorOfPublication.latestForDiscovery3c94748e-c303-4294-ad67-c5a0739628e5
relation.isGoalOfPublication42dc4679-bf07-41ff-b435-3ecfdcf74555
relation.isGoalOfPublication.latestForDiscovery42dc4679-bf07-41ff-b435-3ecfdcf74555
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
IndJPhaEdRes_53_2_268.pdf
Size:
670.43 KB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Yayınlar - Eserler
Eczacılık Fakültesi