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Design of Benzene-1,2-diamines as selective inducible nitric oxide synthase inhibitors: a combined de novo design and docking analysis

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Abstract

Selective inhibition of inducible nitric oxide synthases (iNOS) has been a challenging problem for researchers pursuing work in finding methods to treat inflammatory disorders, shock, etc. Though many inhibitors have been studied to date, all are associated with selectivity or potency problems. Additionally, most of the reported compounds have several similarities and fewer number of novel structures are being tried. There is an increasing need to design novel molecules for this target. In this work, de novo design using LUDI, combined with docking analysis using FlexX has been employed in an attempt to identify novel scaffolds. Benzene-1,2-diamines were identified which could mimic the interactions of the substrate analogs and other inhibitors. Comparative docking scores in each of the isoforms of nitric oxide synthase were employed to recognize hits for iNOS selectivity.

Figure shows the docked poses of the ligand M226 along with that of the reference GW274150. (FlexX analysis)

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Authors and Affiliations

  1. Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar, 160 062, Punjab, India

    Sandrea M. Francis & Manishika Sharma

  2. Department of Pharmaceutical Technology, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar, 160 062, Punjab, India

    Amit Mittal

  3. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar, 160 062, Punjab, India

    Prasad V. Bharatam

Authors
  1. Sandrea M. Francis
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  2. Amit Mittal
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  3. Manishika Sharma
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  4. Prasad V. Bharatam
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Correspondence to Prasad V. Bharatam.

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Francis, S.M., Mittal, A., Sharma, M. et al. Design of Benzene-1,2-diamines as selective inducible nitric oxide synthase inhibitors: a combined de novo design and docking analysis. J Mol Model 14, 215–224 (2008). https://doi.org/10.1007/s00894-007-0263-y

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  • DOI: https://doi.org/10.1007/s00894-007-0263-y

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