MOLECULAR DOCKING, PHARMACOPHORE MODELLING, AND ADME-TOXICITY PREDICTION OF CURCUMIN ANALOG COMPOUNDS AS INFLAMMATORY INHIBITOR ON RHEUMATOID ARTHRITIS


Lutfi Chabib, Rizki Awaluddin, Zullies Ikawati, Ronny Martien, Hilda Ismail

Abstract


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.


Keywords


Molecular docking, Gamavuton (GVT-0), Rheumatoid arthritis, TNF-α, IL-1β

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About this article

Title

MOLECULAR DOCKING, PHARMACOPHORE MODELLING, AND ADME-TOXICITY PREDICTION OF CURCUMIN ANALOG COMPOUNDS AS INFLAMMATORY INHIBITOR ON RHEUMATOID ARTHRITIS

Keywords

Molecular docking, Gamavuton (GVT-0), Rheumatoid arthritis, TNF-α, IL-1β

DOI

10.22159/ijpps.2017v9i9.20450

Date

22-07-2017

Additional Links

Manuscript Submission

Journal

International Journal of Pharmacy and Pharmaceutical Sciences
Vol 9, Issue 9, 2017 Page: 16-21

Online ISSN

0975-1491

Statistics

142 Views | 55 Downloads

Authors & Affiliations

Lutfi Chabib
Faculty of Pharmacy, Gadjah Mada University, Yogyakarta 55281, Indonesia
Indonesia

Rizki Awaluddin
Department of Pharmacy, Islamic University of Indonesia, Yogyakarta 55584, Indonesia
Indonesia

Zullies Ikawati
Faculty of Pharmacy, Gadjah Mada University, Yogyakarta 55281, Indonesia
Indonesia

Ronny Martien
Faculty of Pharmacy, Gadjah Mada University, Yogyakarta 55281, Indonesia
Indonesia

Hilda Ismail
3Curcumin Research Centre, Gadjah Mada University, Yogyakarta 55281, Indonesia
Indonesia


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