Discovery of Glycyrrhiza glabra compounds as potent lymphocyte-specific protein tyrosine kinase inhibitors via in silico approaches

Acute lymphoblastic leukaemia (ALL) is a rapidly progressing malignancy of bone marrow and blood. Dysregulated activity of the pre-T-cell receptor-lymphocyte-specific protein tyrosine kinase (LCK) has been linked to enhanced cell proliferation, contributing to T-cell ALL. LCK inhibition with specific drugs has the potential to reverse treatment resistance and provide a therapeutic option for a significant number of T-ALL patients. In this study, 450 compounds from Glycyrrhiza glabra (G. glabra) were screened against LCK using insilico techniques. The virtual screening and visual inspection of the compounds’ interactions with LCK active site residues revealed that 13 compounds exhibited higher binding affinity than the control molecule. The top four compounds—LTS0002748, LTS0007245, LTS0031098, and LTS0014950—were subjected to detailed interaction analysis, demonstrating their interaction with LCK active site residues and sharing multiple interacting residues with the positive control. Furthermore, these compounds possess favorable drug-like properties and minimal toxicity concerns, making them promising candidates for use as LCK inhibitors in leukaemia treatment. However, additional experimental validation is needed to optimize these compounds as potential LCK inhibitors.