Acta Scientific Pharmaceutical Sciences

Research ArticleVolume 1 Issue 5

3D-QSAR and Pharmacophore Identification Studies Applied to Pyridazin-3-one Derivatives as Potent PDE4 Inhibitors

Edeildo F da Silva-Júnior1,2*, Thiago M de Aquino2 and João X de Araújo-Júnior1,2

1Laboratory of Medicinal Chemistry, Nursing and Pharmacy School, Federal University of Alagoas, Lourival Melo Motta Avenue, Tabuleiro dos Martins, Maceió, Brazil
1Chemistry and Biotechnology Institute, Federal University of Alagoas, Lourival Melo Motta Avenue, Tabuleiro dos Martins, Maceió, Brazil

*Corresponding Author: Edeildo F da Silva-Júnior, Laboratory of Medicinal Chemistry, Federal University of Alagoas, Maceió, Alagoas, Brazil.

Received: September 13, 2017; Published: October 27, 2017

Citation: Edeildo F da Silva-Júnior., et al. “3D-QSAR and Pharmacophore Identification Studies Applied to Pyridazin-3-one Derivatives as Potent PDE4 Inhibitors”. Acta Scientific Pharmaceutical Sciences 1.5 (2018).

Abstract

  Phosphodiesterase-4 (PDE4) is the most predominant subtype of PDEs present in cells. This enzyme is responsible for cAMP-specific inactivation to 5'-AMP via hydrolysis and it has been associated with several inflammatory disorders. The aim of this study was to find molecular features from the pyridazin-3-one class in tentative to elucidate a 3D-Quantitative Structure-Activity Relationship (3D-QSAR) to provide useful information for the design of new compounds. In the present work, we report the (3D-QSAR), Partial Least-Square (PLS) with Leave-One-Out (LOO) as cross-validation method and pharmacophore identification studies. The satisfactory statistical validation (r2 = 0.97 and 0.98, q2 = 0.95 and 0.97, F-test = 89.46 and 341.07, pred_r2 = 0.83 and 0.85) from two mathematical models built was obtained by Multiple Linear Regression (MLR) and Stepwise (SW) methods. In addition, pharmacophore model study revealed the importance of some features (two hydrogen bond acceptor, one hydrogen bond donor, and one aromatic ring). Finally, the correlation analysis between all results provides a solid basis for the future rational design of more active and more selective PDE4 inhibitors.

Keywords:PDE4; Pyridazin-3-one; 3D-QSAR; Pharmacophore Model

Copyright: © 2018 Edeildo F da Silva-Júnior., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.



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