In Silico Evaluation for the Inhibitory Action of Curcumin Derivatives on the CD14 Proteins

Abstract

Background: Autoimmune thyroid diseases (AITD) are a class of immune disorders that target the thyroid gland. Two forms of the disease predominate: Graves’ disease and Hashimoto Thyroiditis. The major symptoms of the diseases include hyperthyroidism and hypothyroidism, respectively. Objectives: One target protein of the immune system that is a hot spot in drug discovery is the CD14 protein (or cluster of differentiation 14). CD14 is a cell membrane protein that is highly expressed in macrophages, monocytes, and neutrophils and is a crucial receptor for gram-negative lipopolysaccharide (LPS). The CD14 monocytes produce high levels of HLA-DR, which may contribute to AITD. Single Nucleotide Polymorphisms (SNPs) in CD14 were previously identified to be risk factors to GD and HT diseases. However, the mechanistic involvement of CD14 protein or its relation to the AITD is not yet clear. Methods: In this study, the researchers shed light on targeting CD14 protein in silico for the aim of alleviating autoimmune thyroid diseases. Docking experiments and ADME/Tox (Absorption, distribution, metabolism and elimination) properties were performed to predict the mechanistic insights for the plausible inhibitory effect of recently produced synthetic derivatives of curcumin on CD14, as well as the estimation of drug likeness and bioavailability. Results: Most of the compounds showed variable levels of inhibition on the CD14 protein and good bioavailability scores. Conclusion: The results indicated that curcumin derivatives could be effective drugs against auto-immune thyroid diseases.