Top

Network Modeling Analysis in Health Informatics and Bioinformatics

Published in:

01-12-2019 | Original Article

Design and prediction of favorable substitution site in trifluorophenyl-substituted homopiperazine, pyrazoline, triazepane derivatives as dipeptidyl peptidase IV Inhibitors: HQSAR and docking studies

Authors: M. C. Sharma, S. Jain

Published in: Network Modeling Analysis in Health Informatics and Bioinformatics | Issue 1/2019

Activate our intelligent search to find suitable subject content or patents.

search-config

AI-assisted search

Off

Abstract

In this study, hologram quantitative structure–activity relationship (HQSAR) and molecular docking studies were performed on a dataset of 108 trifluorophenyl homopiperazine, pyrazoline, and triazepane derivatives as dipeptidyl peptidase IV inhibitors. HQSAR model was obtained using atoms, connection, donor, and acceptor as fragment distinction parameters with fragment size (4–7) using components (q² = 0.738, r² = 0.962). Molecular docking study was performed to identify novel potent inhibitors and the important amino acid residues, which formed an interaction with compound 105, were Ser-631, His-741, Tyr-663, Glu-204, Arg-123 and Ala-655 with receptor. These models were used to design new compounds for homopiperazine, pyrazoline, triazepane analogs and the results obtained from this study could be useful for further investigations.

previous article Using multiple network alignment for studying connectomes

next article Melanoma risk modeling from limited positive samples

Dont have a licence yet? Then find out more about our products and how to get one now:

Springer Professional "Wirtschaft+Technik"

Online-Abonnement

Mit Springer Professional "Wirtschaft+Technik" erhalten Sie Zugriff auf:

über 102.000 Bücher
über 537 Zeitschriften

aus folgenden Fachgebieten:

Automobil + Motoren
Bauwesen + Immobilien
Business IT + Informatik
Elektrotechnik + Elektronik
Energie + Nachhaltigkeit
Finance + Banking
Management + Führung
Marketing + Vertrieb
Maschinenbau + Werkstoffe
Versicherung + Risiko

Jetzt Wissensvorsprung sichern!

inform now

Springer Professional "Technik"

Online-Abonnement

Mit Springer Professional "Technik" erhalten Sie Zugriff auf:

über 67.000 Bücher
über 390 Zeitschriften

aus folgenden Fachgebieten:

Automobil + Motoren
Bauwesen + Immobilien
Business IT + Informatik
Elektrotechnik + Elektronik
Energie + Nachhaltigkeit
Maschinenbau + Werkstoffe

Jetzt Wissensvorsprung sichern!

inform now

Springer Professional "Wirtschaft"

Online-Abonnement

Mit Springer Professional "Wirtschaft" erhalten Sie Zugriff auf:

über 67.000 Bücher
über 340 Zeitschriften

aus folgenden Fachgebieten:

Bauwesen + Immobilien
Business IT + Informatik
Finance + Banking
Management + Führung
Marketing + Vertrieb
Versicherung + Risiko

Jetzt Wissensvorsprung sichern!

inform now

Ahn JH, Park WS, Jun MA, Shin MS, Kang SK, Kim KY, Rhee SD, Bae MA, Kim KR, Kim SG, Kim SY, Sohn SK, Kang NS, Lee JO, Lee DH, Cheon HG, Kim SS (2008) Synthesis and biological evaluation of homopiperazine derivatives with beta-aminoacyl group as dipeptidyl peptidase IV inhibitors. Bioorg Med Chem Lett 18:6525–6529CrossRef

Ahrén B, Holst JJ, Mårtensson H, Balkan B (2000) Improved glucose tolerance and insulin secretion by inhibition of dipeptidyl peptidase IV in mice. Eur J Pharmacol 404(1–2):239–245CrossRef

Al-Najjar BO, Wahab HA, Tengku Muhammad TS, Shu-Chien AC, Ahmad Noruddin NA, Taha MO (2011) Discovery of new nanomolar peroxisome proliferator-activated receptor gamma activators via elaborate ligand-based modeling. Eur J Med Chem 46(6):2513–2529CrossRef

Augustyns K, Van Der Veken P, Senten K et al (2003) Dipeptidyl peptidase IV inhibitors as new therapeutic agents for the treatment of type 2 diabetes. Expert Opin Ther Pat 13(4):499–510CrossRef

Bush BL, Nachbar RB (1993) Sample-distance partial least squares: PLS optimized for many variables, with application to CoMFA. J Comput Aided Mol Des 7(5):587–619CrossRef

Conarello SL, Li Z, Ronan J, Roy RS, Zhu L, Jiang G, Liu F, Woods J, Zycband E, Moller DE, Thornberry NA, Zhang BB (2003) Mice lacking dipeptidyl peptidase IV are protected against obesity and insulin resistance. Proc Natl Acad Sci 100(11):6825–6830CrossRef

Cramer RD, Patterson DE, Bunce JD (1988) Comparative Molecular-Field Analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins. J Am Chem Soc 110:5959–5967CrossRef

Demuth H, Heins J (1995) Catalytic mechanism of dipeptidyl peptidase-IV. In: dipeptidyl peptidase-IV (CD26) in metabolism and the immune response. Fleischer B, Landes RG (eds) Austin, TX, vol. 3, pp 1–35

Flower DR (1998) On the properties of bit string-based measures of chemical similarities. J Chem Inf Comput Sci 38:379–386CrossRef

Heritage TW, Lowis DR (1999) Molecular hologram QSAR. In: Rational drug design: novel methodology and practical applications. Oxford University Press, New York

Jun MA, Park WS, Kang SK, Kim KY, Kim KR, Rhee SD, Bae MA, Kang NS, Sohn SK, Kim SG, Lee JO, Lee DH, Cheon HG, Kim SS, Ahn JH (2008) Synthesis and biological evaluation of pyrazoline analogues with beta-amino acyl group as dipeptidyl peptidase IV inhibitors. Eur J Med Chem 43:1889–1902CrossRef

Klebe G, Abraham U, Mietzner T (1994) Molecular similarity indexes in a comparative-analysis (comsia) of drug molecules to correlate and predict their biological-activity. J Med Chem 37:4130–4146CrossRef

Lowis DR (1997) HQSAR: a new, highly predictive QSAR technique. Tripos Tech Notes 1(5):17

Marguet D (2000) Enhanced insulin secretion and improved glucose tolerance in mice lacking CD26. Proc Natl Acad Sci 97(12):6874–6879CrossRef

Mentlein R (1999) Dipeptidyl-peptidase IV (CD26)-role in the inactivation of regulatory peptides. Regul Pept 85:9–24CrossRef

Mest HJ, Mentlein R (2005) Dipeptidyl peptidase inhibitors as new drugs for the treatment of type 2 diabetes. Diabetologia 48(4):616–620CrossRef

Nordhoff S, López-Canet M, Hoffmann-Enger B, Bulat S, Cerezo-Gálvez S, Hill O, Rosenbaum C, Rummey C, Thiemann M, Matassa VG, Edwards PJ, Feurer A (2009) From lead to preclinical candidate optimization of beta-homophenylalanine based inhibitors of dipeptidyl peptidase IV. Bioorg Med Chem Lett 19:4818–4823CrossRef

Park WS, Jun MA, Shin MS, Kwon SW, Kang SK, Kim KY, Dal Rhee S, Bae MA, Narsaiah B, Lee DH, Cheon HG, Ahn JH, Kim SS (2009) Synthesis and biological evaluation of triazepane derivatives as DPP-IV inhibitors. J Fluor Chem 130:1001–1010CrossRef

Ping L, Chen WN, Chen WM (2011) Molecular modeling studies on imidazo[4,5- b]pyridine derivatives as Aurora A kinase inhibitors using 3D-QSAR and docking approaches. Eur J Med Chem 46:77–94CrossRef

Pospisilik JA, Stafford SG, Demuth HU, Brownsey R, Parkhouse W, Finegood DT, McIntosh CH, Pederson RA (2002) Long-term treatment with the dipeptidyl peptidase IV inhibitor P32/98 causes sustained improvements in glucose tolerance, insulin sensitivity, hyperinsulinemia, and beta-cell glucose responsiveness in VDF (fa/fa) Zucker rats. Diabetes 51(4):943–950CrossRef

Saqib U, Siddiqi MI (2009) 3D-QSAR studies on triazolopiperazine amide inhibitors of dipeptidyl peptidase-IV as anti-diabetic agents SAR QSAR. Environ Res 20:519–535

Sebokova E, Christ AD, Boehringer M, Mizrahi J (2007) Dipeptidyl peptidase IV inhibitors: the next generation of new promising therapies for the management of type 2 diabetes. Curr TopMed Chem 7:547–555CrossRef

Sharma MC, Jain S, Sharma R (2018) Trifluorophenyl -based inhibitors of dipeptidyl peptidase-IV as antidiabetic agents: 3D-QSAR COMFA, CoMSIA methodologies. Netw Model Anal Health Inform Bioinform 7:1. https://doi.org/10.1007/s13721-017-0163-8 CrossRef

Sonawane L, Bari S (2011) Ligand-based in silico 3D-QSAR study of PPAR-γ agonists. Med Chem Res 20(7):1005–1014CrossRef

Tong W, Lowis DR, Perkins R, Chen Y, Welsh WJ, Goddette DW, Heritage TW, Sheehan DM (1998) Evaluation of quantitative structure–activity relationship methods for large-scale prediction of chemicals binding to the estrogen receptor. J Chem Inf Comput Sci 38:669–677CrossRef

Yang XL, Zhou Y, Liu XL (2014) Hologram quantitative structure–activity relationship studies on 1-(5-carboxyindol-1-yl) propan-2-one inhibitors of human cytosolic phospholipase A2α. Med Chem Res 23(3):1512–1518CrossRef

Yaron A, Nadier F (1993) Proline-Dependent Structural and Biological Properties of Peptides and Proteins. Crit Rev Biochem Mol Biol 28:31–81CrossRef

Yasuda N, Nagakura T, Yamazaki K et al (2002) Improvement of high fat-diet-induced insulin resistance in dipeptidyl peptidase IV-deficient Fischer rats. Life Sci 71(2):227–238CrossRef

Zeng J, Liu G, Tang Y, Jiang H (2007) 3D-QSAR studies on fluoropyrrolidine amides as dipeptidyl peptidase IV inhibitors by CoMFA and CoMSIA. J Mol Model 13:993–1000CrossRef

Title: Design and prediction of favorable substitution site in trifluorophenyl-substituted homopiperazine, pyrazoline, triazepane derivatives as dipeptidyl peptidase IV Inhibitors: HQSAR and docking studies
Authors: M. C. Sharma
S. Jain
Publication date: 01-12-2019
Publisher: Springer Vienna
Published in: Network Modeling Analysis in Health Informatics and Bioinformatics / Issue 1/2019
Print ISSN: 2192-6662
Electronic ISSN: 2192-6670
DOI: https://doi.org/10.1007/s13721-019-0184-6

Springer Professional

Abstract

Please log in to get access to your license.

Dont have a licence yet? Then find out more about our products and how to get one now:

Springer Professional "Wirtschaft+Technik"

Springer Professional "Technik"

Springer Professional "Wirtschaft"

Other articles of this Issue 1/2019

Chronic fatigue syndrome: identification of transcription factor (TFs) associated with gene expression for drug signature prediction

Melanoma risk modeling from limited positive samples

Review of topics related to autism spectrum disorder on Twitter

A new approach (EDIZ) for big data variant prioritization

Identification of target genes in cancer diseases using protein–protein interaction networks

Regional patterning of co-expressed genes in autistic brains

Premium Partner