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Inventi Rapid - Molecular Modeling

Articles

  • Inventi:pmm/25721/18
    IN-SILICO INDUCED-FIT DOCKING STUDY OF SOME DECAHYDROPHENANTHREN-ONE DERIVATIVES AS POTENTIAL 5-LOX INHIBITORS
    Tomy Muringayil Joseph*, Debarshi Kar Mahapatra

    5-LOX play a pivotal role in the synthesis of leukotrienes (LTs) which is a potent inflammatory mediator. The strategies for the control of inflammatory responses involved inhibition of the 5-LOX which will directly inhibit the LTs production, thereby resulting in complete management of disease like asthma, allergic rhinitis, psoriasis, rheumatoid arthritis and colitis ulcerosa. The existing interesting study represents a committed effort for investigating the 5-LOX inhibitory potential (PDB ID: 1N8Q) by in-silico induced-fit molecular docking techniques employing Maestro 9.1 software for two low-molecular-weight ligands of decahydrophenanthren-one scaffold; (4bS,7S,8aS)-1,1,4b-trimethyl-7-vinyl-1,4b,5,6,7,8,8a,9,10,10a-decahydrophenanthren-3(2H)-one (1) and (2R,4aR,7R,10aS)-7-hydroxy-2-vinyl-2,3,4a,4b,5,6,7,8,10,10a-decahydrophenanthren -4(1H)-one (2). The present study represented an attempt of developing future NSAIDs of decahydrophenanthren-one scaffold with LMWL perspective which will have the capability to inhibit the essential inflammatory mediators. The ligand 1 exhibited Glide Score of -10.01 Kcal/mol by interacting with the Ile857 residue of the active site of 5-LOX. The ligand 2 expressed better Glide Score of -10.70 Kcal/mol by interacting with the active site amino acid residue Gln716. From the study, it was recognized that the position of the substituents and their type is crucial in inhibiting the target. The position of the carbonyl on the third ring and the hydroxyl group in the first ring has been identified to be crucial for inhibiting 5-LOX. Therefore, the present study opened new avenues of developing low-molecular-weight anti-inflammatory agents with better pharmacokinetic and pharmacodynamics attributes.

    How to Cite this Article
    Tomy Muringayil Joseph, Debarshi Kar Mahapatra. In-Silico Induced-Fit Docking Study of Some Decahydrophenanthren-One Derivatives as Potential 5-LOX Inhibitors. Inventi Rapid: Molecular Modeling, 2018(3):1-3, 2018.
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