Synthesis, characterization, crystal structure of novel bis-thiomethylcyclohexanone derivatives and their inhibitory properties against some metabolic enzymes
Bioorganic Chemistry, vol.82, pp.393-404, 2019 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 82
- Publication Date: 2019
- Doi Number: 10.1016/j.bioorg.2018.11.001
- Journal Name: Bioorganic Chemistry
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Page Numbers: pp.393-404
- Keywords: Acetylcholinesterase, Bis-thiomethylcyclohexanone, Carbonic anhydrase, Crystal structure
- Bilecik Şeyh Edebali University Affiliated: No
Abstract
In this study, a series of novel bis-thiomethylcyclohexanone compounds (3a–3j) were synthesized by the addition of thio-Michael to the bis-chalcones under mild reaction conditions. The bis-thiomethylcyclohexanone derivatives (bis-sulfides) were characterized by 1H NMR, 13C NMR, FTIR and elemental analysis techniques. Furthermore, the molecular and crystal structures of 3h, 3i and 3j compounds were determined by single crystal X-ray diffraction studies. In this study, X-ray crystallography provided an alternative and often-complementary means for elucidating functional groups at the enzyme inhibitory site. Acetylcholinesterase (AChE) is a member of the hydrolase protein super family and has a significant role in acetylcholine-mediated neurotransmission. Here, we report the synthesis and determining of novel bis-thiomethylcyclohexanone compounds based hybrid scaffold of AChE inhibitors. The newly synthesized bis-thiomethylcyclohexanone compounds showed Ki values of in range of 39.14–183.23 nM against human carbonic anhydrase I isoenzyme (hCA I), 46.03–194.02 nM against human carbonic anhydrase II isoenzyme (hCA II), 4.55–32.64 nM against AChE and 12.77–37.38 nM against butyrylcholinesterase (BChE). As a result, novel bis-thiomethylcyclohexanone compounds can have promising anti Alzheimer drug potential and record novel hCA I, and hCA II enzymes inhibitor.