Synthesis, characterization, evaluation of metabolic enzyme inhibitors and in silico studies of thymol based 2-amino thiol and sulfonic acid compounds.

Autor: Bora RE; Department of Chemistry, Faculty of Sciences, Erciyes University, 38039, Kayseri, Turkey. Electronic address: rifatbora@erciyes.edu.tr., Genc Bilgicli H; Department of Chemistry, Faculty of Sciences, Sakarya University, 54050, Sakarya, Turkey. Electronic address: hayriyegenc@sakarya.edu.tr., Üç EM; Department of Chemistry, Faculty of Sciences, Ataturk University, 25240, Erzurum, Turkey. Electronic address: edamehtap3@gmail.com., Alagöz MA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, İnonu University, 44280, Malatya, Turkey. Electronic address: mehmet.alagoz@inonu.edu.tr., Zengin M; Department of Chemistry, Faculty of Sciences, Sakarya University, 54050, Sakarya, Turkey. Electronic address: mzengin@sakarya.edu.tr., Gulcin İ; Department of Chemistry, Faculty of Sciences, Ataturk University, 25240, Erzurum, Turkey. Electronic address: igulcin@atauni.edu.tr.
Jazyk: angličtina
Zdroj: Chemico-biological interactions [Chem Biol Interact] 2022 Oct 01; Vol. 366, pp. 110134. Date of Electronic Publication: 2022 Aug 31.
DOI: 10.1016/j.cbi.2022.110134
Abstrakt: Eight new aminothiols (4a-g and 5) and three new sulfonic acid derivatives (6a-c) were synthesized, and their structures were characterized. Inhibitory effects of the obtained compounds on carbonic anhydrase I and II isoforms (hCA I and hCA II), butyrylcholinesterase (BChE) and acetylcholinesterase (AChE), enzymes were investigated. The newly synthesized compounds have inhibited hCA I with K i s ranging from 7.11 ± 1.46 nM (6a) to 670.52 ± 300.41 nM (4b) and, hCA II with K i s ranging from 16.83 ± 5.72 nM (6a) to 453.34 ± 208.56 nM (4c). Acetazolamide was employed as the positive control for both hCA isoforms (K i for hCA I 198.81 ± 14.13 nM and K i for hCA II 211.42 ± 13.10 nM), and among the new compounds obtained, it was observed that there were compounds that were active at much lower nM levels. All compounds were also evaluated for inhibition of AChE and BChE. They inhibited AChE and BChE enzymes in the range of Ki 5.24 ± 2.27 (6c) - 48.44 ± 21.82 (4g) for AChE and 4.86 ± 0.64 (6c) - 51.75 ± 12.56 (4a) for BChE, and the results were compared with the standard inhibitor Tacrine (K i : 14.20 ± 8.83 nM toward AChE and K i : 3.39 ± 1.91 nM for BChE). Cholinesterase (BChE and AChE) inhibitory abilities of all synthesized molecules were also performed in situ and molecular docking and molecular dynamics (MD) simulation studies. The molecular coupling scores of the compounds and the free binding energies calculated by MM/GBSA were found to be compatible. Examining the results obtained from this study shows that it may have the potential to develop new drugs to treat some global patients such as glaucoma and Alzheimer's disease (AD).
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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