Curcumin analogs as the inhibitors of TLR4 pathway in inflammation and their drug like potentialities: a computer-based study
| Autor: | Md. Hasanur Rahman, Md. Asad Ullah, Bishajit Sarkar, Yusha Araf, Fatema Tuz Johora |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Drug Lipopolysaccharides Curcumin medicine.drug_class media_common.quotation_subject Catechols Computational biology IκB kinase Protein Serine-Threonine Kinases Biochemistry Anti-inflammatory 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Computational Chemistry Diarylheptanoids medicine Humans Receptor Molecular Biology media_common Inflammation Kinase Guaiacol NF-kappa B Cell Biology I-kappa B Kinase Toll-Like Receptor 4 030104 developmental biology chemistry Pharmaceutical Preparations Docking (molecular) Cyclooxygenase 2 030220 oncology & carcinogenesis TLR4 Fatty Alcohols Signal Transduction |
| Zdroj: | Journal of receptor and signal transduction research. 40(4) |
| ISSN: | 1532-4281 |
| Popis: | Toll-like receptor 4 (TLR4) pathway is one of the major pathways that mediate the inflammation in human body. There are different anti-inflammatory drugs available in the market which specifically act on different signaling proteins of TLR4 pathway but they do have few side effects and other limitations for intended use in human body. In this study, Curcumin and its different analogs have been analyzed as the inhibitors of signaling proteins, i.e. Cycloxygenase-2 (COX-2), inhibitor of kappaβ kinase (IKK) and TANK binding kinase-1 (TBK-1) of TLR4 pathway using different computational tools. Initially, three compounds were selected for respective target based on free binding energy among which different compounds were reported to have better binding affinity than commercially available drug (control). Upon continuous computational exploration with induced fit docking (IFD), 6-Gingerol, Yakuchinone A and Yakuchinone B were identified as the best inhibitors of COX-2, IKK, and TBK-1 respectively. Then their drug-like potentialities were analyzed in different experiments where they were also predicted to perform well. Hopefully, this study will uphold the efforts of researchers to identify anti-inflammatory drugs from natural sources. |
| Databáze: | OpenAIRE |
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