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Articles

Vol. 2 No. 3 (2011): July – September 2011

Molecular Modeling Studies of β-aminoacyl containing Homopiperazine derivatives as DPP4 Inhibitors

DOI
https://doi.org/10.37285/ijddd.2.3.4
Submitted
December 9, 2024
Published
2024-12-09

Abstract

Dipeptidyl peptidase IV (DPP4) is a promising target for developing novel anti-diabetic and anti-obesity drugs. Pharmacophore based three dimensional quantitative structure activity relationship studies (3D-QSAR) and molecular docking were performed on a series of 56 β-aminoacyl-containing homopiperazine derivatives of DPP4 inhibitors to find out the structural relationship with the activity. The best predictive 3D-QSAR model with pharmacophore based alignment resulted in R2 (training set) value of 0.9407, Q2 (internal test set) value of 0.9053, Pearson-R value of 0.9517 and root mean square error (RMSE) 0.2838. The information rendered by pharmacophore based 3D-QSAR models and docking studies may afford valuable clues to optimize the lead and design of potent, selective inhibitors.

References

  1. [1] Yaron, A.; Naider F. Crit Rev Biochem Mol Biol, 1993, 28, 31.
  2. [2] Mentlein, R. Regul Pept, 1999, 85, 9.
  3. [3] Deacon, CF.; Ahrén, B.; Holst, JJ. Expert Opin Investig Drugs, 2004, 13,1091.
  4. [4] Rosenblum, JS.; Kozarich, JW. Curr Opin Chem Biol. 2003, 7, 496.
  5. [5] Lankas, GR.; Leiting, B.; Roy, RS.; Eiermann, GJ.;, Beconi, MG.; Biftu, T.; Chan, CC.; Edmondson, S.; Feeney, WP.; He, H.; Ippolito, DE.;, Kim, D.; Lyons, KA.; Ok, HO.; Patel, RA.; Petrov, AN.; Pryor, KA.; Qian, X.; Reigle, L.; Woods, A.; Wu, JK.; Zaller, D.; Zhang,X.; Zhu, L.; Weber, AE.; Thornberry, NA, Diabetes, 2005, 54, 2988.
  6. [6] 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, Bioorg Med Chem Lett, 2008,18, 6525.
  7. [7] Liang, GB.; Qian, X.; Feng, D.; Biftu, T.; Eiermann, G.; He, H.; Leiting, B.; Lyons, K.; Petrov, A.; Sinha-Roy.; R, Zhang, B.; Wu, J.; Zhang, X.; Thornberry, NA.; Weber AE, Bioorg Med Chem Lett, 2007,17,1903.
  8. [8] Biftu, T.; Feng, D.; Qian, X.; Liang, GB.; Kieczykowski, G.; Eiermann, G.; He, H.; Leiting, B.; Lyons, K.; Petrov, A.; Sinha-Roy, R.; Zhang, B.; Scapin, G.; Patel, S.; Gao, YD.; Singh, S.; Wu J.; Zhang, X.; Thornberry, NA.; Weber, AE, Bioorg Med Chem Lett, 2007, 17, 49.
  9. [9] McFarland, JW.; Gans, DJ, Quant. Struct-Act Relat, 1994, 13, 11.
  10. [10] Schrödinger, LLC, New York, NY 2009.
  11. [11] Still, WC.; Tempczyk, A.; Hawley, RC.; Hendrickson, T, J Am Chem, 1990, 112, 6127.
  12. [12] Friesner, RA.; Banks, JL.; Murphy, RB.; Halgren, TA.; Klicic, JJ.; Mainz, DT.; Repasky, MP.; Knoll, EH.; Shelley, M.; Perry, JK.; Shaw, DE.; Francis, P.; Shenkin, PS, J Med Chem, 2004, 47, 1739.
  13. [13] Halgren, TA.; Murphy, RB.; Friesner, RA.; Beard, HS.; Frye, LL.; Pollard, WT.; Banks, JL, J Med Chem, 2004, 47, 750.
  14. [14] Friesner, RA.; Murphy, RB.; Repasky, MP.; Frye, LL.; Greenwood, JR.; Halgren, TA.; Sanschagrin, PC.; Mainz, DT, J Med Chem, 49, 2006, 6177.
  15. [15] Dixon, SL.; Smondyrev, AM.; Knoll, EH.; Rao, SN.; Shaw, DE, Friesner, RA. J Comput Aided Mol Des, 2006, 20,647.
  16. [16] DeLano, WL, The PyMOL Molecular Graphics System, version 0.98. DeLano Scientific, San Carlos, CA, US. Available on http://www.pymol.org.