Generic placeholder image

Letters in Drug Design & Discovery


ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

General Research Article

The Impacts of Some Sedative Drugs on α -Glycosidase, Acetylcholinesterase and Butyrylcholinesterase Enzymes-potential Drugs for Some Metabolic Diseases

Author(s): Ruya Kaya, Parham Taslimi*, Muhammet Emin Naldan and İlhami Gulçin

Volume 16, Issue 5, 2019

Page: [592 - 596] Pages: 5

DOI: 10.2174/1570180815666180924110023

Price: $65


Background: The present paper focuses on the in vitro inhibition of some sedative drugs such as Midazolam, Propofol, Hipnodex, Ketamine, and Pental sodium on acetylcholinesterase (AChE), Butyrylcholinesterase (BChE), and α-glycosidase (α-Gly) enzymes.

Methods: These drugs were tested in diverse concentrations, which showed positive effects in vitro AChE, BChE, and α-Gly activities. Ki values were 20.14, 94.93, 636.78, 416.42, and 953.75 µM for AChE, 17.52, 32.03, 88.02, 93.48, and 91.84 µM for BChE, and 10.87, 156.68, 48.21, 37.88, 151.01 µM for α-glycosidase, respectively.

Results: An enhancing number of experiential observations show potentially harmful effects of sedative drugs on the extension of brain.

Conclusion: Midazolam exhibited effective inhibitory activity compared with the other drugs for these enzymes.

Keywords: Sedative drugs, α-glycosidase, acetylcholinesterase, butyrylcholinesterase, enzyme inhibition, propofol, midazolam.

Graphical Abstract
Tobias, J.D. Dexmedetomidine to treat opioid withdrawal in infants following prolonged sedation in the pediatric ICU. J. Opioid. Management., 2006, 2, 201-205.
Szumita, P.M.; Baroletti, S.A.; Anger, K.E.; Wechsler, M.E. Sedation and analgesia in the intensive care unit: Evaluating the role of dexmedetomidine. Am. J. Health Syst. Pharm., 2007, 64, 37-44.
Coates, D.P.; Prys-Roberts, C.; Spelina, K.R.; Monk, C.R.; Norley, I. Propofol (‘Diprivan’) by intravenous infusion with nitrous oxide: Dose requirements and haemodynamic effects. Postgrad. Med. J., 1985, 61, 76-79.
Gülçin, I.; Ahmet, A.H.; Cesur, M. Determination of in vitro antioxidant and radical scavenging activities of propofol. Chem. Pharm. Bull., 2005, 53, 281-285.
Nicol, M.E.; Moriarty, J.; Edwards, J. Modification of pain on injection of propofol-a comparison between lignocaine and procaine. Anaesthesia, 1991, 46, 67-69.
Parker, R.I.; Mahan, R.A.; Giugliano, D.; Parker, M.M. Efficacy and safety of intravenous midazolam and ketamine as sedation for therapeutic and diagnostic procedures in children. Pediatrics, 1997, 99, 427-431.
Cugini, U.; Lanzetta, P.; Nadbath, P.; Menchini, U. Sedation with ketamine during cataract surgery. J. Cataract Refract. Surg., 1997, 23, 784-786.
Gross, J.B.; Blouin, R.T.; Zandsberg, S.; Conard, P.F.; Häussler, J. Effect of flumazenil on ventilatory drive during sedation with midazolam and alfentanil. Anesthesiology, 1996, 85, 713-720.
Oztaskın, N.; Çetinkaya, Y.; Taslimi, P. Antioxidant and acetylcholinesterase inhibition properties of novel bromophenol derivatives. Bioorg. Chem., 2015, 60, 49-57.
Özbey, F.; Taslimi, P.; Gulcin, I.; Maraş, A.; Göksu, S.; Supuran, C.T. Synthesis of diaryl ethers with acetylcholinesterase, butyrylcholinesterase and carbonic anhydrase inhibitory actions. J. Enzyme Inhib. Med. Chem., 2016, 31, 79-85.
Aksu, K.; Özgeris, B.; Taslimi, P.; Naderi, A.; Gülçin, İ.; Göksu, S. Antioxidant activity, acetylcholinesterase, and carbonic anhydrase inhibitory properties of novel ureas derived from phenethylamines. Arch. Pharm, 2016, 349, 944-954.
Bayrak, Ç.; Taslimi, P.; Gulcin, I. The first synthesis of 4-phenylbutenone derivative bromophenols including natural products and their inhibition profiles for carbonic anhydrase, acetylcholinesterase and butyrylcholinesterase enzymes. Bioorg. Chem., 2017, 72, 359-366.
Pistrosch, F.; Schaper, F.; Passauer, J. Effects of the alpha glucosidase inhibitor acarbose on endothelial function after a mixed meal in newly diagnosed type 2 diabetes. Horm. Metab. Res., 2009, 41, 104-108.
Hanefeld, M.; Schaper, F.; Koehler, C. Effect of acarbose on vascular disease in patients with abnormal glucose tolerance. Cardiovasc. Drugs Ther., 2008, 22, 225-231.
Shimabukuro, M.; Higa, N.; Chinen, I.; Yamakawa, K.; Takasu, N. Effects of a single administration of acarbose on postprandial glucose excursion and endothelial dysfunction in type 2 diabetic patients: a randomized crossover study. J. Clin. Endocrinol. Metab., 2006, 91, 837-842.
Martin, A.E.; Montgomery, P.A. Acarbose: An alpha-glucosidase inhibitor. Am. J. Health Syst. Pharm., 1996, 53, 2277-2290.
Ellman, G.L.; Courtney, K.D.; Andres, V. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmaco l., 1961, 7, 88-95.
Akıncıoğlu, A.; Akıncıoğlu, H.; Gülçin, I.; Durdagi, S.; Supuran, C.T.; Göksu, S. Discovery of potent carbonic anhydrase and acetylcholine esterase inhibitors: Novel sulfamoylcarbamates and sulfamides derived from acetophenones. Bioorg. Med. Chem., 2015, 23, 3592-3602.
Polat, K.L.; Gülçin, I.; Gören, A.C.; Namiesnik, J.; Martinez-Ayala, A.L.; Gorinstein, S. LC-MS/MS analysis, antioxidant and anticholinergic properties of galanga (Alpinia officinarum Hance) rhizomes. Ind. Crops Prod., 2015, 74, 712-721.
Taslimi, P.; Sujayev, A.; Garibov, E. Synthesis of new cyclic thioureas and evaluation of their metal-chelating activity, acetylcholinesterase, butyrylcholinesterase, and carbonic anhydrase inhibition profiles. J. Biochem. Mol. Toxicol., 2017, 31, e21897.
Koçyiğit, U.M.; Taslimi, P.; Gezegen, H.; Gulçin, İ.; Ceylan, M. Evaluation of acetylcholinesterase and carbonic anhydrase inhibition profiles of 1,2,3,4,6-pentasubstituted-4-hydroxy-cyclohexanes. J. Biochem. Mol. Toxicol., 2017, 31, e21938.
Öztaşkın, N.; Taslimi, P.; Maraş, A.; Gülcin, İ.; Göksu, S. Novel antioxidant bromophenols with acetylcholinesterase, butyrylcholinesterase and carbonic anhydrase inhibitory actions. Bioorg. Chem., 2017, 74, 104-114.
Koçyiğit, U.M.; Taşkıran, A.; Taslimi, P.; Yokuş, A.; Temel, Y.; Gulçin, İ. Inhibitory effects of oxytocin and oxytocin receptor antagonist atosiban on the activities of carbonic anhydrase and acetylcholinesterase enzymes in the liver and kidney tissues of rats. J. Biochem. Mol. Toxicol., 2017, 31, e21972.
Gulçin, İ.; Abbasova, M.; Taslimi, P.; Huyut, Z.; Safarova, L.; Sujayev, A.; Farzaliyev, V.; Beydemir, Ş.; Alwasel, S.H.; Supuran, C.T. 7.Synthesis and biological evaluation of aminomethyl and alkoxymethyl derivatives as carbonic anhydrase, acetylcholinesterase and butyrylcholinesterase inhibitors. J. Enzyme Inhib. Med. Chem., 2017, 32, 1174-1182.
Tao, Y.; Zhang, Y.; Cheng, Y. Rapid screening and identification of α-glucosidase inhibitors from mulberry leaves using enzyme-immobilized magnetic beads coupled with HPLC/MS and NMR. Biomed. Chrom., 2013, 27, 148-155.
Akıncioglu, H.; Gülçin, I.; Alwasel, S.H. Investigation of inhibitory effect of humic acid on acetylcholinesterase and butyrylcholinesterase enzymes. Fresen Environ. Bull., 2017, 26, 3733-3739.
Taslimi, P.; Akıncıoğlu, H.; Gulçin, İ. Synephrine and phenylephrine act as α-amylase, α-glycosidase, acetylcholinesterase, butyrylcholinesterase, and carbonic anhydrase enzymes inhibitors. J. Biochem. Mol. Toxicol., 2017, 31, e21973.
Lineweaver, H.; Burk, D. The Determination of Enzyme Dissociation Constants. J. Am. Chem. Soc., 1934, 56, 658-566.
Smith, P.F.; Darlington, C.L. The behavioral effects of long-term use of benzodiazepine sedative and hypnotic drugs: what can be learned from animal studies? New Zealand. J. Psychol., 1994, 23, 48-63.
Riker, R.R.; Shehabi, Y.; Bokesch, P.M. Dexmedetomidine vs midazolam for sedation of critically ill patients: A randomized trial. JAMA, 2009, 301, 489-499.
Ye, X.P.; Song, C.Q.; Yuan, P. α-Glucosidase and α-amylase inhibitory activity of common constituents from traditional Chinese medicine used for diabetes mellitus. Chin. J. Nat. Med., 2010, 8, 349-352.
Özgeriş, B.; Göksu, S.; Köse Polat, L.; Gülçin, İ.; Salmas, R.E.; Durdagi, S.; Tümer, F.; Supuran, C. T7 Acetylcholinesterase and carbonic anhydrase inhibitory properties of novel urea and sulfamide derivatives incorporating dopaminergic 2-aminotetralin scaffolds. Bioorg. Med. Chem., 2016, 24, 2318-2329.
Gülçin, İ.; Scozzafava, A.; Supuran, C.T. The effect of caffeic acid phenethyl ester (CAPE) on metabolic enzymes including acetylcholinesterase, butyrylcholinesterase, glutathione Stransferase, lactoperoxidase, and carbonic anhydrase isoenzymes I, II, IX, and XII. J. Enzyme Inhib. Med. Chem., 2016, 31, 1095-1101.
Benalla, W.; Bellahcen, S.; Bnouham, M. Antidiabetic medicinal plants as a source of alpha glucosidase inhibitors. Curr. Diab. Rev., 2010, 6, 247-254.
Taslimi, P.; Gulçin, İ. Antioxidant and anticholinergic properties of olivetol. J. Food Biochem., 2018, 42, e12516.
Colovic, M.B.; Krstic, D.Z.; Lazarevic-Pasti, T.D.; Bondzic, A.M.; Vasic, V.M. Acetylcholinesterase inhibitors: Pharmacology and toxicology. Curr. Neuropharmacol., 2013, 11, 315-335.
Behcet, A.; Çağlılar, T.; Barut Celepci, D.; Aktaş, A.; Taslimi, P.; Gök, Y.; Aygün, M.; Kaya, R.; Gulçin, İ. Synthesis, characterization and crystal structure of 2-(4-hydroxyphenyl)ethyl and 2-(4-nitrophenyl)ethyl substituted benzimidazolium bromide salts: their ınhibitory properties against carbonic anhydrase and acetylcholinesterase. J. Mol. Struc., 2018, 1170, 160-169.
Koçak, R.; Turan, A.E.; Kalin, P.; Oktay, T. Synthesis of some novel norbornene-fused pyridazines as potent inhibitors of carbonic anhydrase and acetylcholinesterase. J. Heterocyc. Chem., 2016, 53, 2049-2056.
Aksu, K.; Özgeriş, B.; Taslimi, P. Antioxidant activity, acetylcholinesterase, and carbonic anhydrase inhibitory properties of novel ureas derived from phenethylamines. Arch. Pharm., 2016, 349, 944-954.
Işık, M.; Beydemir, S.; Yılmaz, A.; Naldan, M.E.; Aslan, H.E.; Gülçin, İ. Oxidative stress and mRNA expression of acetylcholinesterase in the leukocytes of ischemic patients. Biomed. Pharmacother., 2017, 87, 561-567.
Tabet, N. Acetylcholinesterase Inhibitors for Alzheimer’s disease: Anti-inflammatories in acetylcholine clothing! Age Ageing, 2006, 35, 336-338.
Day, K.E.; Scott, L.M. Use of acetylcholinesterase activity to detect sublethal toxicity in stream iuvertebrates exposed to low coucentrations of organophosphate iusecticides. Aquat. Toxicol., 1990, 18, 101-114.
Nemcsok, J.; Orban, L.; Dobber, L. Acetylcholinesterase activity measurements as a tool for demonstrating the possible cause of fish decay. Acta Biol. Szeged., 1985, 31, 9-12.

Rights & Permissions Print Export Cite as
© 2024 Bentham Science Publishers | Privacy Policy