Open AccessMOLECULAR DOCKING, PHARMACOPHORE MODELLING, AND ADME-TOXICITY PREDICTION OF CURCUMIN ANALOG COMPOUNDS AS INFLAMMATORY INHIBITOR ON RHEUMATOID ARTHRITIS
Author(s) -
Lutfi Chabib,
Rizki Awaluddin,
Zullies Ikawati,
Ronny Martien,
Hilda Ismail
Publication year - 2017
Publication title -
international journal of pharmacy and pharmaceutical sciences/international journal of pharmacy and pharmaceutical sciences
Language(s) - English
Resource type - Journals
eISSN - 2656-0097
pISSN - 0975-1491
DOI - 10.22159/ijpps.2017v9i9.20450
Subject(s) - adme , pharmacophore , curcumin , pharmacology , chemistry , toxicity , tumor necrosis factor alpha , rheumatoid arthritis , enzyme , docking (animal) , biochemistry , drug , medicine , immunology , nursing , organic chemistry
Objective: The objective of this research was to examine the activity and cytokine inhibitory mechanism of curcumin analog compound against multiple protein targets in a patient with rheumatoid arthritis (RA) and identify the absorption, distribution, metabolism, excretion and toxicity (ADME-toxicity).Methods: Identification was carried out by in silico through pharmacophore modelling using Ligand Scout, molecular docking using iGemDock in various protein (tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), transcription factors, signalling kinase, and cyclooxygenase enzyme) and identification of ADME-toxicity based on the physicochemical properties of the compound to simulate, predict and analyze interaction between protein and compound.Results: The obtained results indicated that gamavuton (GVT-0) and penta-gamavuton (PGV) possessed high bioavailability with lower toxicity than curcumin. However, GVT-0, a curcumin analog, possessed high and specific inhibitory activity on tumor necrosis factor-α converting enzyme (TACE) and interleukin converting enzyme (ICE)/Caspase-1.Conclusion: GVT-0 as a curcumin derivate possessed the best inhibitory activity against TNF-α converting enzyme and IL-1β converting enzyme which are the main route of inflammatory mediators in rheumatoid arthritis. In addition, GVT-0 influences less in metabolism of CYP450 enzymes, and has low toxicity.