Curcumin analogs as the inhibitors of TLR4 pathway in inflammation and their drug like potentialities: a computer-based study

Abstract

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.

Keywords:

• Anti-inflammatory
• curcumin
• inflammation
• inhibitor
• TLR4

Acknowledgments

Authors acknowledge the members of Swift Integrity Computational Lab, Dhaka, Bangladesh, a virtual platform of young researchers for their support during the preparation of the manuscript.

Disclosure statement

Authors declare no conflict of interest regarding the publication of the manuscript.

Data availability

Authors made all the data generated during experiment and analysis available within the manuscript.

Additional information

Funding

Authors received no specific funding from any external sources.