SAR Evaluation of Disubstituted Tacrine Analogues as Promising Cholinesterase and Carbonic Anhydrase Inhibitors
| Autor: | Salih Okten, Makbule Ekiz, Ahmet Tutar, Burcu Butun, Umit Muhammet Kocyigit, Gulactı Topcu, Ilhami Gulcin |
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| Přispěvatelé: | Okten, S, Ekiz, M, Tutar, A, Butun, B, Kocyigit, UM, Topcu, G, Gulcin, I, Sakarya Üniversitesi/Fen-Edebiyat Fakültesi/Kimya Bölümü, Tutar, Ahmet, Kırıkkale Üniversitesi, BÜTÜN, Burcu, [Okten, Salih] Kirikkale Univ, Fac Educ, Dept Maths & Sci Educ, Yahsihan, Kirikkale, Turkey -- [Ekiz, Makbule -- Tutar, Ahmet] Sakarya Univ, Fac Art & Sci, Dept Chem, TR-54187 Serdivan, Sakarya, Turkey -- [Butun, Burcu] Bezmialem Vakif Univ, Fac Pharm, Dept Pharmaceut Chem, TR-34093 Istanbul, Turkey -- [Kocyigit, Umit Muhammet] Cumhuriyet Univ, Vocat Sch Hlth Serv, Dept Med Tech, TR-58140 Sivas, Turkey -- [Topcu, Gulacti] Bezmialem Vakif Univ, Fac Pharm, Dept Pharmacognosy Phytochem, TR-34093 Istanbul, Turkey -- [Gulcin, Ilhami] Ataturk Univ, Fac Sci, Dept Chem, TR-25240 Erzurum, Turkey, Okten, Salih -- 0000-0001-9656-1803 |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Carbonic anhydrase
biology Chemistry Tacrine derivatives Pharmacology ÖKTEN 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 Anticholinegic Tacrine Butyrylcholinesterase medicine biology.protein Acetylcholinesterase Pharmacology & Pharmacy General Pharmacology Toxicology and Pharmaceutics medicine.drug Cholinesterase SAR |
| Popis: | WOS: 000466869900012 Background: 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. Sakarya University Research Fund [2014-0204-008] This study was supported by grants from the Sakarya University Research Fund (Project number: 2014-0204-008). |
| Databáze: | OpenAIRE |
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