In Silico Study and Validation of Natural Compounds Derived from Macleaya cordata as a Potent Inhibitor for BTK

Abstract

Bruton’s tyrosine kinase (BTK) is a kinase of the TEC family expressed in B cells and other hematopoietic cells, but it is not expressed in T cells. B-cell malignancies such as multiple myeloma and chronic lymphocytic leukemia have been shown to have a high expression of BTK, thereby displaying oncogenic activities in these diseases, triggering the discovery of BTK inhibitors. The study investigated computationally the phytochemical present in M cordata as a novel BTK inhibitor with high efficacy in treating B-cell malignancies. Chelidimerine, Bocconarborine A, and Bocconarborine B show a high binding affinity of −13.7, −13.3, and −12.9, respectively. This study was validated using molecular dynamic stimulation to indicate the stability and interaction of the ligand with the targeted protein. Bocconarborine B has the best binding energy of −30.94 kcal/mol compared to ibrutinib, with a binding energy of −22.46 kcal/mol. The identified hit compounds from this study were subjected to half maximum inhibitory concentration prediction (IC₅₀) using machine learning modeling; the result shows that Bocconarborine B has the best IC₅₀ of 48.98 nM. This study is subject to validation via in vivo and in vitro studies.

Keywords

machine learning modeling / B-cell malignancies / Bocconarborine B / ibrutinib / molecular dynamic simulation

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