Title: Identification of dual target anti-inflammatory inhibitors using merged structure-based pharmacophore modelling and docking approach

Authors: Manikandan Selvaraj; Muhd Hanis Md Idris; Siti Norhidayu Mohd Amin; Mohd Zaki Salleh; Teh Lay Kek

Addresses: Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM), Bandar Puncak Alam, 42300 Selangor, Malaysia ' Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM), Bandar Puncak Alam, 42300 Selangor, Malaysia ' Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM), Bandar Puncak Alam, 42300 Selangor, Malaysia ' Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM), Bandar Puncak Alam, 42300 Selangor, Malaysia; Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Bandar Puncak Alam, 42300 Selangor, Malaysia ' Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM), Bandar Puncak Alam, 42300 Selangor, Malaysia; Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Bandar Puncak Alam, 42300 Selangor, Malaysia

Abstract: Merged structure-based pharmacophore modelling followed by 3D database search and molecular docking were the sequential protocol applied in order to identify selective novel COX-2 and PDE4D as dual target anti-inflammatory inhibitors. Utilisation of the key interaction features of crystal structures of COX-2 (pdb: 1CX2) and PDE4D (pdb: N0YN) was exploited as critical component in the selection of dual target inhibitors. Through this approach, nine chalcone and flavones scaffold-like compounds were selected as putative dual target anti-inflammatory inhibitors from Asinex database. In general, understanding such approach could provide valuable insights into discovery of novel anti-inflammatory inhibitors as therapeutic agents.

Keywords: anti-inflammatory inhibitors; COX; cyclooxygenase; docking; dual target; merged pharmacophore model; PDE; phosphodiesterase.

DOI: 10.1504/IJCBDD.2018.094626

International Journal of Computational Biology and Drug Design, 2018 Vol.11 No.3, pp.183 - 191

Received: 07 Feb 2017
Accepted: 10 Jul 2017
Published online: 10 Sep 2018 *

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