Synthesis,characterization, crystal structure of novel bis-thiomethylcyclohexanone derivatives and their inhibitory properties against some metabolic enzymes |
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Affiliation: | 1. Department of Chemistry, Faculty of Science, Akdeniz University, 07058 Antalya, Turkey;2. Department of Chemistry, Faculty of Science, Atatürk University, 25240 Erzurum, Turkey;3. Serik Gülsün Süleyman Sural Vocational School of Higher Education, Department of Opticianry Program, Akdeniz University, 07058 Antalya, Turkey;4. Central Research Laboratory, İzmir Katip Çelebi University, 35620 İzmir, Turkey;5. Faculty of Pharmacy, Ağrı İbrahim Çeçen University, 04100 Agrı, Turkey;1. Atatürk University, Faculty of Science, Department of Chemistry, Erzurum, Turkey;2. Agri İbrahim Çeçen University, Central Researching Laboratory, Agri, Turkey;3. Computational Biology and Molecular Simulations Laboratory, Department of Biophysics, School of Medicine, Bahcesehir University, 34349 Istanbul, Turkey;5. Dipartimento di Chimica Ugo Schiff, Universita degli Studi di Firenze, Sesto Fiorentino, Firenze, Italy;6. Neurofarba Department, Section of Pharmaceutical and Nutriceutical Sciences, Universita degli Studi di Firenze, Sesto Fiorentino, Florence, Italy;1. Department of Chemistry, Faculty of Science, Ataturk University, 25240 Erzurum, Turkey;2. Department of Biotechnology, Faculty of Science, Bartin University, 74100 Bartin, Turkey;1. Department of Maths and Science Education, Faculty of Education, Kırıkkale University, Yahşihan, 71450, Kırıkkale, Turkey;2. Department of Chemistry, Faculty of Art and Science, Sakarya University, Serdivan, 54187, Sakarya, Turkey;3. Vocational School of Health Services, Cumhuriyet University, 58140, Sivas, Turkey;4. Department of Physics, Faculty of Sciences, Cumhuriyet University, 58140, Sivas, Turkey;5. Department of Physics, Faculty of Sciences, Erciyes University, 38039, Kayseri, Turkey;6. Department of Chemistry, Faculty of Sciences, Ataturk University, 25240, Erzurum, Turkey;1. Department of Chemistry, Faculty of Science and Art, Adiyaman University, 02040 Adıyaman, Turkey;2. Department of Chemistry, Faculty of Sciences, Ataturk University, 25240 Erzurum, Turkey;3. Agri Ibrahim Cecen University, Central Research and Application Laboratory, 04100 Agri, Turkey;4. Department of Molecular Biology and Genetics, Faculty of Arts and Science, Kilis 7 Aralik University, 79000 Kilis, Turkey;5. Advanced Technology Application and Research Center, Kilis 7 Aralik University, 79000 Kilis, Turkey;6. Department of Chemistry, Faculty of Art and Science, Inonu University, 44260 Malatya, Turkey;1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Selcuk University, Konya, Turkey;2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Atatürk University, Erzurum, Turkey;3. Department of Chemistry, Faculty of Science, Atatürk University, Erzurum, Turkey;4. Neurofarba Department, Section of Pharmaceutical and Nutriceutical Sciences, Universita degli Studi di Firenze, Florence, Italy |
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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. |
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Keywords: | Bis-thiomethylcyclohexanone Carbonic anhydrase Acetylcholinesterase Crystal structure |
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