Virtual Screening through Molecular Docking Analysis to Identify Potential Natural Inhibitor(s) of Lyn Tyrosine Kinase- An In-silico Approach

Abstract

Breast cancer on becoming one of the leading cancer types, emerged as an important barrier in increasing life expectancy of the overall population. In the current study, some compounds were screened based on literature survey for the identification of natural bioactive compounds as potential inhibitors of Lyn tyrosine kinase. Therefore, a multi-step molecular docking was carried out using AutoDock embedded in the MGL Tools. After initial screening, molecules having a higher docking score and binding free energy compared to Tamoxifen were considered for further assessment. Some already known synthetic lyn tyrosine kinase inhibitor have been used for better understanding of the comparative study. Based on in silico Lipinski filter analysis, toxicity prediction, pharmacokinetic analysis, four compounds were proposed to be promising inhibitors of Lyn tyrosine kinase. Furthermore, the binding interactions of all proposed inhibitors of Lyn showed strong ligand efficiency in terms of energy score obtained with the help of molecular modelling analyses. Hence, the proposed compounds out of which three are bioactive compounds might be taken forward as potential next-generation Lyn kinase inhibitors for managing Lyn associated breast cancer after experimental authentication.

Baicalein alleviates fibrosis and inflammation in systemic sclerosis by regulating B-cell abnormalities

“…Recent studies have shown the relationship between baicalein and immune cells to counteract fibrosis, such as the downregulation of expression of proinflammatory cytokines and chemokines (e.g., interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha (TNF-α) and monocyte chemoattractant protein-1 (MCP-1)) [ 13 ] and inhibition of infiltration of inflammatory cells (macrophages and lymphocytes) [ 26 ]. Baicalein has been identified as an inhibitor of Lyn kinase [ 27 ], which is the first signal-transducing kinase required for B cell activation in SSc patients [ 28 ] and contributes to the development of systemic autoimmunity and skin sclerosis through CD19-dependent pathway in tight skin mice [ 29 ]. Moreover, spleen tyrosine kinase (Syk) is another tyrosine kinase after B cell receptor (BCR) activation which is involved in the sclerodermatous process via B cell signaling [ 30 ].…”