Research Article | Volume: 11, Supplement 1, March, 2021

Design, synthesis, and evaluation of some novel N-benzothiazol-2-yl benzamide derivatives as allosteric activators of human glucokinase

Sandeep Arora Ajmer Singh Grewal Neelam Sharma Kunal Arora Ervon Dhalio Sukhbir Singh   

Open Access   

Published:  Feb 11, 2021

DOI: 10.7324/JAPS.2021.11s104
Abstract

Some newer benzamide analogues of N-benzothiazol-2-yl were prepared and assessed for human glucokinase (GK) activation accompanied by molecular docking investigations for predicting the bonding connections of the these derivatives with residues in the allosteric site of GK. Among the derivatives synthesized, 6 and 7 strongly increased the catalytic action of GK (GK activation fold about 2.0 compared to control) in vitro. The outcomes of in vitro assay were supported by the molecular docking investigations of these analogues with allosteric site residues of the GK protein. Derivatives investigated in the present study can afford few lead compounds for the discovery of harmless and strong allosteric GK activating compounds for the management of type 2 diabetes.


Keyword:     Benzamides benzothiazole derivatives docking glucokinase GK activators in silico GK assay


Citation:

Arora S, Grewal AS, Sharma N, Arora K, Dhalio E, Singh S. Design, synthesis, and evaluation of some novel N-benzothiazol-2-yl benzamide derivatives as allosteric activators of human glucokinase. J Appl Pharm Sci, 2021; 11 (Supp 1):038–047.

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

HTML Full Text

Reference

Bastaki S. Diabetes mellitus and its treatment. Int J Diabetes Metab, 2005; 13:111-34. https://doi.org/10.1159/000497580

Bowler JM, Hervert KL, Kearley ML, Miller BG. Smallmolecule allosteric activation of human glucokinase in the absence of glucose. ACS Med Chem Lett, 2013; 4(7):580-4. https://doi.org/10.1021/ml400061x

Charaya N, Pandita D, Grewal AS, Lather V. Design, synthesis and biological evaluation of novel thiazol-2-yl benzamide derivatives as glucokinase activators. Comput Biol Chem, 2018; 73:221-9. https://doi.org/10.1016/j.compbiolchem.2018.02.018

Coghlan M, Leighton B. Glucokinase activators in diabetes management. Expert Opin Investig Drugs, 2008; 17(2):145-67. https://doi.org/10.1517/13543784.17.2.145

Efanov AM, Barrett DG, Brenner MB, Briggs SL, Delaunois A, Durbin JD, Giese U, Guo H, Radloff M, Gil GS, Sewing S, Wang Y, Weichert A, Zaliani A, Gromada J. A novel glucokinase activator modulates pancreatic islet and hepatocyte function. Endocrinology, 2005; 146(9):3696-701. https://doi.org/10.1210/en.2005-0377

Ericsson H, Sjoberg F, Heijer M, Dorani H, Johansson P, Wollbratt M, Norjavaara E. The glucokinase activator AZD6370 decreases fasting and postprandial glucose in type 2 diabetes mellitus patients with effects influenced by dosing regimen and food. Diabetes Res Clin Pract, 2012; 98:436-44. https://doi.org/10.1016/j.diabres.2012.09.025

Futamura M, Hosaka H, Kadotani A, Shimazaki H, Sasaki K, Ohyama S, Nishimura T, Eiki J, Nagata Y. An allosteric activator of glucokinase impairs the interaction of glucokinase and glucokinase regulatory protein and regulates glucose metabolism. J Biol Chem, 2006; 281:37668-74. https://doi.org/10.1074/jbc.M605186200

Grewal AS, Beniwal M, Pandita D, Sekhon BS, Lather M. Recent updates on peroxisome proliferator-activated receptor δ agonists for the treatment of metabolic syndrome. Med Chem, 2016a; 12:03-21. https://doi.org/10.2174/1573406411666150525105826

Grewal AS, Bhardwaj S, Pandita D, Lather V, Sekhon BS. Updates on aldose reductase inhibitors for management of diabetic complications and non-diabetic diseases. Mini Rev Med Chem, 2016b; 16(2):120-62. https://doi.org/10.2174/1389557515666150909143737

Grewal AS, Dua, JS, Prasad DN, Kharb R, Lather V. Design, synthesis and evaluation of novel 3,5-disubstituted benzamide derivatives as allosteric glucokinase activators. BMC Chem, 2019a; 13:2. https://doi.org/10.1186/s13065-019-0532-8

Grewal AS, Kharb R, Dua JS, Lather V. Molecular docking assessment of N-heteroaryl substituted benzamide derivatives as glucokinase activators. Asian J Pharm Pharmacol, 2019b; 5(1):129-36. https://doi.org/10.31024/ajpp.2019.5.1.18

Grewal AS, Kharb R, Prasad DN, Dua JS, Lather V. N-Pyridin2-yl benzamide analogues as allosteric activators of glucokinase: design, synthesis, in vitro, in silico and in vivo evaluation. Chem Biol Drug Des, 2019c; 93:364-72. https://doi.org/10.1111/cbdd.13423

Grewal AS, Lather V, Pandita D, Bhayana G. Synthesis, docking and biological evaluation of phenylacetic acid and trifluoromethylphenyl substituted benzamide derivatives as potential PPARδ agonists. Lett Drug Des Discov, 2017; 14:1239-51. https://doi.org/10.2174/1570180814666170327164443

Grewal AS, Sekhon BS, Lather V. Recent updates on glucokinase activators for the treatment of type 2 diabetes mellitus. Mini Rev Med Chem, 2014; 14:585-602. https://doi.org/10.2174/1389557514666140722082713

Kohei K. Pathophysiology of type 2 diabetes and its treatment policy. Japan Med Assoc J, 2010; 53:41-6.

Lagorce D, Bouslama L, Becot J, Miteva MA, Villoutreix BO. FAF-Drugs4: free ADME-tox filtering computations for chemical biology and early stages drug discovery. Bioinformatics, 2017; 33:3658-60. https://doi.org/10.1093/bioinformatics/btx491

Lei L, Liu Q, Liu S, Huan Y, Sun S, Chen Z, Li L, Feng Z, Li Y, Shen Z. Antidiabetic potential of a novel dual-target activator of glucokinase and peroxisome proliferator activated receptor-γ. Metab Clin Exp, 2015; 64(10):1250-61. https://doi.org/10.1016/j.metabol.2015.06.014

Matschinsky FM, Zelent B, Doliba N, Li C, Vanderkooi JM, Naji A, Sarabu R, Grimsby J. Glucokinase activators for diabetes therapy. Diabetes Care, 2011; 34:S236-43. https://doi.org/10.2337/dc11-s236

McKerrecher D, Steven A. Design and development of the glucokinase activator AZD1656. In: Abdel-Magid AF, Pesti JA, Vaidyanathan R (eds.). Complete accounts of integrated drug discovery and development: recent examples from the pharmaceutical industry. Washington, DC: American Chemical Society, pp 185-220, 2018. https://doi.org/10.1021/bk-2018-1307.ch007

Miteva M, Guyon F, Tufféry P. Frog2: efficient 3D conformation ensemble generator for small compounds. Nucl Acids Res, 2010; 38: W622-7. https://doi.org/10.1093/nar/gkq325

Miteva M, Violas S, Montes M, Gomez D, Tuffery P, Villoutreix B. FAF-drugs: free ADME/Tox filtering of compound collections. Nucl Acids Res, 2006; 34:W738-44. https://doi.org/10.1093/nar/gkl065

Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ. AutoDock4 and AutoDockTools4: automated docking with selective receptor flexiblity. J Comput Chem, 2009; 16: 2785-91. https://doi.org/10.1002/jcc.21256

Olokoba AB, Obateru OA, Olokoba LB. Type 2 diabetes mellitus: a review of current trends. Oman Med J, 2012; 27:269-73. https://doi.org/10.5001/omj.2012.68

Pal M. Medicinal chemistry approaches for glucokinase activation to treat type 2 diabetes. Curr Med Chem, 2009a; 16(29):3858-74. https://doi.org/10.2174/092986709789177993

Pal M. Recent advances in glucokinase activators for the treatment of type 2 diabetes. Drug Discov Today, 2009b; 14:784-92. https://doi.org/10.1016/j.drudis.2009.05.013

Park K, Lee BM, Hyun KH, Lee DH, Choi HH, Kim H, Chong W, Kim KB, Nam SY. Discovery of 3-(4-methanesulfonylphenoxy)-N-[1- (2-methoxy-ethoxymethyl)-1H-pyrazol-3-yl]-5-(3-methylpyridin-2-yl)- benzamide as a novel glucokinase activator (GKA) for the treatment of type 2 diabetes mellitus. Bioorg Med Chem, 2014; 22(7):2280-93. https://doi.org/10.1016/j.bmc.2014.02.009

Park K, Lee BM, Kim YH, Han T, Yi W, Lee DH, Choi HH, Chong W, Lee CH. Discovery of a novel phenylethyl benzamide glucokinase activator for the treatment of type 2 diabetes mellitus. Bioorg Med Chem Lett, 2013; 23(2):537-42. https://doi.org/10.1016/j.bmcl.2012.11.018

Perseghin G. Exploring the in vivo mechanisms of action of glucokinase activators in type 2 diabetes. J Clin Endocrinol Metab, 2010; 95(11):4871-3. https://doi.org/10.1210/jc.2010-2049

Pike KG, Allen JV, Caulkett PWR, Clarke DS, Donald CS, Fenwick ML, Johnson KM, Johnstone C, McKerrecher D, Rayner JW, Walker RP, Wilson I. Design of a potent, soluble glucokinase activator with increased pharmacokinetic half-life. Bioorg Med Chem Lett, 2011; 21(11):3467-70. https://doi.org/10.1016/j.bmcl.2011.03.093

Pires DE, Blundell TL, Ascher DB. pkCSM: Predicting smallmolecule pharmacokinetic and toxicity properties using graph-based signatures. J Med Chem, 2015; 58(9):4066-72. https://doi.org/10.1021/acs.jmedchem.5b00104

Pires DE, Kaminskas LM, Ascher DB. Prediction and optimization of pharmacokinetic and toxicity properties of the ligand. Methods Mol Biol, 2018; 1762:271-84. https://doi.org/10.1007/978-1-4939-7756-7_14

Rathee D, Grewal AS, Dureja H, Lather V. Enzymatic inhibitory activity of iridoid glycosides from Picrorrhiza kurroa against matrix metalloproteinases: correlating in vitro targeted screening and docking. Comput Biol Chem, 2019; 78:28-36. https://doi.org/10.1016/j.compbiolchem.2018.10.017

Salgueiro A, Folmer V, da Rosa H, Costa M, Boligon A, Paula F, Roos D, Puntel G. In vitro and in silico antioxidant and toxicological activities of achyrocline satureioides. J Ethnopharmacol, 2016; 194:6-14. https://doi.org/10.1016/j.jep.2016.08.048

Singh R, Lather V, Pandita D, Judge V, Arumugam KN, Grewal AS. Synthesis, docking and antidiabetic activity of some newer benzamide derivatives as potential glucokinase activators. Lett Drug Des Discov, 2017; 14:540-53. https://doi.org/10.2174/1570180813666160819125342

Sjostrand M, Ericsson H, Hartford M, Norjavaara E, Eriksson JW. Pharmacodynamic effects of the oral glucokinase activator AZD6370 after single doses in healthy volunteers assessed with euglycaemic clamp. Diabetes Obes Metab, 2013; 15(1):35-41. https://doi.org/10.1111/j.1463-1326.2012.01672.x

Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. J Comput Chem, 2010; 31:455-61. https://doi.org/10.1002/jcc.21334

Wang Z, Shi X, Zhang H, Yu L, Cheng Y, Zhang H, Zhang H, Zhou J, Chen J, Shen X, Duan W. Discovery of cycloalkyl-fused N-Thiazol2-yl-benzamides as tissue non-specific glucokinase activators: design, synthesis, and biological evaluation. Eur J Med Chem, 2017; 139:128-52. https://doi.org/10.1016/j.ejmech.2017.07.051

Article Metrics
531 Views 40 Downloads 571 Total

Year

Month

Related Search

By author names