Login Register Cart 0
Generic placeholder image

Current Computer-Aided Drug Design

Editor-in-Chief

ISSN (Print): 1573-4099
ISSN (Online): 1875-6697

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

In silico Molecular Docking Study to Search New SGLT2 Inhibitor based on Dioxabicyclo[3.2.1] Octane Scaffold

Author(s): Shubham Kumar, Gopal L. Khatik and Amit Mittal*

Volume 16, Issue 2, 2020

Page: [145 - 154] Pages: 10

DOI: 10.2174/1573409914666181019165821

Price: $65

Abstract

Background: Diabetes is a leading cause of high mortality rate in the world. Recently, SGLT2 inhibitors showed the promising result to treat diabetes and therefore several molecules are approved by the US FDA.

Objective: SGLT2 inhibitors were designed based on dioxabicyclo[3.2.1] octane with the aim to search new lead molecule.

Methods: The molecular structures were drawn in ChemBiodraw ultra and molecular docking study was performed by AutoDock Vina 1.5.6 software. The LogP and toxicity were predicted online using AlogP and Lazar in-silico respectively.

Results: Among all the designed molecules, SK306 showed the maximum binding affinity against the 3dh4 SGLT2 protein of Vibrio parahaemolyticus. LogP values were also calculated in order to determine the lipophilic property of the best binding molecules which show LogP 2.82-3.79 in the range for good absorption and elimination, also predicted to be non-toxic.

Conclusion: SGLT2 inhibitors were designed based on the dioxabicyclo [3.2.1] octane resulting in a new lead molecule with high binding affinity; also these molecules were predicted to be noncarcinogenic with low LogP.

Keywords: SGLT2 inhibitors, AutoDock Vina, molecular docking, diabetes, dioxabicyclo[3.2.1] octane, Vibrio parahaemolyticus.

« Previous Next »
Graphical Abstract

[1]
Ogurtsova, K.; da Rocha Fernandes, J.D.; Huang, Y.; Linnenkamp, U.; Guariguata, L.; Cho, N.H.; Cavan, D.; Shaw, J.E.; Makaroff, L.E. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res. Clin. Pract., 2017, 128, 40-50.
[http://dx.doi.org/10.1016/j.diabres.2017.03.024] [PMID: 28437734 ]
[2]
Ramachandran, U.; Kumar, R.; Mittal, A. Fine tuning of PPAR ligands for type 2 diabetes and metabolic syndrome. Mini Rev. Med. Chem., 2006, 6(5), 563-573.
[http://dx.doi.org/10.2174/138955706776876140] [PMID: 16719831 ]
[3]
Bharatam, P.V.; Patel, D.S.; Adane, L.; Mittal, A.; Sundriyal, S. Modeling and informatics in designing anti-diabetic agents. Curr. Pharm. Des., 2007, 13(34), 3518-3530.
[http://dx.doi.org/10.2174/138161207782794239] [PMID: 18220788 ]
[4]
Bolen, S.; Feldman, L.; Vassy, J.; Wilson, L.; Yeh, H.C.; Marinopoulos, S.; Wiley, C.; Selvin, E.; Wilson, R.; Bass, E.B.; Brancati, F.L. Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus. Ann. Intern. Med., 2007, 147(6), 386-399.
[http://dx.doi.org/10.7326/0003-4819-147-6-200709180-00178] [PMID: 17638715 ]
[5]
Vasilakou, D.; Karagiannis, T.; Athanasiadou, E.; Mainou, M.; Liakos, A.; Bekiari, E.; Sarigianni, M.; Matthews, D.R.; Tsapas, A. Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes: a systematic review and meta-analysis. Ann. Intern. Med., 2013, 159(4), 262-274.
[http://dx.doi.org/10.7326/0003-4819-159-4-201308200-00007] [PMID: 24026259 ]
[6]
Baker, W.L.; Smyth, L.R.; Riche, D.M.; Bourret, E.M.; Chamberlin, K.W.; White, W.B. Effects of sodium-glucose co-transporter 2 inhibitors on blood pressure: a systematic review and meta-analysis. J. Am. Soc. Hypertens., 2014, 8(4), 262-275.
[http://dx.doi.org/10.1016/j.jash.2014.01.007] [PMID: 24602971 ]
[7]
Bołdys, A.; Okopień, B. Inhibitors of type 2 sodium glucose co-transporters--a new strategy for diabetes treatment. Pharmacol. Rep., 2009, 61(5), 778-784.
[http://dx.doi.org/10.1016/S1734-1140(09)70133-1] [PMID: 19904000]
[8]
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204042 orig1s000approv.pdf (accessed Jan 18, 2018).
[9]
FDA approves empagliflozin for adults with type 2 diabetes, https://www.mdedge.com/clinicalendocrinologynews/article/86161/diabetes/fda-approves-empagliflozin-adults-type-2-diabetes (accessed Jan 18, 2018).
[10]
Study of Ipragliflozin in patients with type 2 diabetes mellitus receiving insulin therapy - full text view - clinicaltrials.gov https://www.clinicaltrials.gov/ct2/show/NCT02847091?term=ipragliflozin&rank=2 (accessed Jan 18, 2018).
[11]
Poole, R.M.; Prossler, J.E. Tofogliflozin: first global approval. Drugs, 2014, 74(8), 939-944.
[http://dx.doi.org/10.1007/s40265-014-0229-1] [PMID: 24848755 ]
[12]
Markham, A.; Elkinson, S. Luseogliflozin: first global approval. Drugs, 2014, 74(8), 945-950.
[http://dx.doi.org/10.1007/s40265-014-0230-8] [PMID: 24848756 ]
[13]
Efficacy and safety of sotagliflozin versus placebo in patients with type 2 diabetes mellitus not currently treated with antidi-abetic therapy - full text view - clinicaltrials.gov https://www.clinicaltrials. gov/ct2/show/NCT02926937?term=sotagliflozin&rank=2 (accessed Jan 19, 2018).
[14]
Safety and efficacy of biphasic Remogliflozin etabonate in the treatment of type 2 diabetes - full text view - clinicaltrials.gov https://www.clinicaltrials.gov/ct2/show/NCT02537470?term=Remogliflozin&rank=1 (accessed Jan 19, 2018).
[15]
Sergliflozin Etabonate - Pharmacodia http://en.pharmacodia.com/ web/drug/1_3392.html (accessed Jan 19, 2018).
[16]
Kaur, K.; Kaur, P.; Mittal, A.; Nayak, S.; Khatik, G. Design and Molecular docking studies of novel antimicrobial peptides using autodock molecular docking software. Asian J. Pharm. Clin. Res., 2017, 10, 28-32.
[http://dx.doi.org/10.22159/ajpcr.2017.v10s4.21332]
[17]
Chaurasiya, S.; Kaur, P.; Nayak, S.K.; Khatik, G.L. Virtual screening for identification of novel potent EGFR inhibitors through AutoDock Vina molecular modeling software. J. Chem. Pharm. Res., 2016, 8, 353-360.
[18]
Trott, O.; Olson, A.J. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem., 2010, 31(2), 455-461.
[PMID: 19499576 ]
[19]
Energy minimizations were performed MM2 interface program on ChemBio3D Ultra 12.0, and structures were drawn by ChemBio- Drwa Ultra 12.0; Cambridge Soft: Cambridge 1985.
[20]
Abramson, J.; Faham, S.; Cascio, D. Crystal structure of sodium/ Sugar symporter with bound ga-lactose from vibrio parahaemolyticus https://www.rcsb.org/structure/3DH4
[21]
AlogP values were calculated by: http://146.107.217.178/web/ alogps/ (accessed Jan 31, 2018)
[22]
Lazar toxicity predictions: https://lazar.in-silico.ch/predict (accessed Jan 31, 2018)
[23]
Li, Y.; Shi, Z.; Chen, L.; Zheng, S.; Li, S.; Xu, B.; Liu, Z.; Liu, J.; Deng, C.; Ye, F. Discovery of a potent, selective renal sodium-dependent glucose cotransporter 2 (SGLT2) Inhibitor (HSK0935) for the treatment of type 2 diabetes. J. Med. Chem., 2017, 60(10), 4173-4184.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01818] [PMID: 28447791 ]
[24]
Razzaghi-Asl, N.; Sepehri, S.; Ebadi, A.; Miri, R.; Shahabipour, S. Molecular docking and quantum mechanical studies on bioflavonoid structures as BACE-1 inhibitors. Struct. Chem., 2015, 26(2), 607-621.
[http://dx.doi.org/10.1007/s11224-014-0523-2]
[25]
da Silva-Junior, E.F.; Barcellos Franca, P.H.; Ribeiro, F.F.; Bezerra Mendonca-Junior, F.J.; Scotti, L.; Scotti, M.T.; de Aquino, T.M.; de Araujo-Junior, J.X. Molecular Docking Studies Applied to a Dataset of Cruzain Inhibitors. Curr. Comput. Aided Drug Des., 2018, 14(1), 68-78.
[http://dx.doi.org/10.2174/1573409913666170519112758] [PMID: 28523999 ]
[26]
Leo, A.; Hansch, C.; Elkins, D. Partition coefficients and their uses. Chem. Rev., 1971, 71, 525-616.
[http://dx.doi.org/10.1021/cr60274a001]

Rights & Permissions Print Cite
Article Metrics
33
2
© 2024 Bentham Science Publishers | Privacy Policy