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Medicinal Chemistry Research

, Volume 23, Issue 10, pp 4542–4558 | Cite as

3D-QSAR and molecular docking studies of 1,3,4-oxadiazoles containing substituted phenoxy fragment as inhibitors of enoyl-acyl carrier protein reductase from Escherichia coli

  • Shrinivas D. JoshiEmail author
  • Sheshagiri R. Dixit
  • Uttam A. More
  • K. V. S. N. Raju
  • Ramanuj Narayan
  • Tejraj M. Aminabhavi
  • Venkatarao H. Kulkarni
Original Research

Abstract

The antibacterial target, enoyl-acyl carrier protein (ACP) reductase, is a homotetrameric enzyme that catalyzes the last reductive step of fatty acid biosynthesis. In the present paper, Surflex docking and 3D-QSAR studies viz., CoMFA and topomer CoMFA have been carried out on a series (53 compounds) of enoyl ACP reductase inhibitors. An alignment rule for the compounds was defined using the database in SYBYL-X 2.0 package (Tripos Inc., St. Louis, USA, 2012). Models were validated using a data set obtained by dividing the data set into training set and test set. From the CoMFA, topomer CoMFA models, steric and electrostatic maps were generated to analyze the structural features of the datasets to indicate that data are well fitted with high predictive ability and inhibitory potency. The best predictions were obtained with CoMFA model (q 2 = 0.403, \(r^{ 2}_{\text{pred}} = 0. 8 3 2\)) and topomer CoMFA model (q 2 = 0.540, \(r^{ 2}_{\text{pred}} = 0. 8 9 9\)). These models and Surflex-docking studies revealed that the ether linkage, hydroxyl group, and 1,3,4-oxadiazole were significant for binding to the receptor, and some essential features were identified to deduce some interesting SARs. Comparisons of results obtained from both the methods have helped in the understanding of specific activity of some compounds.

Graphical Abstract

Molecular modeling studies of 1,3,4-oxadiazoles containing substituted phenoxy fragments as enoyl ACP reductase inhibitors Database alignment for enoyl ACP reductase inhibitors.

Keywords

Enoyl ACP reductase Surflex docking QSAR: CoMFA Topomer CoMFA Phenoxy-1,3,4-oxadiazole derivatives 

Notes

Acknowledgments

The authors gratefully acknowledge the financial support from the Council of Scientific and Industrial Research, New Delhi, India (Letter No. 02(0139)/13/EMR-II dated-12/04/2013). We thank Mr. H. V. Dambal, President, S.E.T’s College of Pharmacy, Dharwad, India, for providing the facilities. The authors are grateful to Mr. Ravi N. Nadiger for his technical assistance.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Shrinivas D. Joshi
    • 1
    Email author
  • Sheshagiri R. Dixit
    • 1
  • Uttam A. More
    • 1
    • 2
  • K. V. S. N. Raju
    • 3
  • Ramanuj Narayan
    • 3
  • Tejraj M. Aminabhavi
    • 1
  • Venkatarao H. Kulkarni
    • 1
  1. 1.Novel Drug Design and Discovery Laboratory, Department of Pharmaceutical ChemistryS.E.T.’s College of PharmacyDharwadIndia
  2. 2.Centre for Research and DevelopmentPrist UniversityThanjavurIndia
  3. 3.Division of Polymers and Functional Materials CSIR-Indian Institute of Chemical TechnologyHyderabadIndia

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