Docking, Molecular Dynamic Simulation and ADMET Analysis of Novel Honokiol Derivatives against Breast Cancer Target Protein LKB1

Breast cancer is characterized by an uncontrolled cell growth in the breast tissue and is a leading cause of death globally. Cytotoxic effects and reduced efficacy of currently used therapeutics insist to look for new chemo-preventive strategies against breast cancer. LKB1 gene has recently been categorized as a tumor suppressor gene where it’s inactivation can cause sporadic carcinomas in various tissues, including the breast. Mutations in the highly conserved LKB1 catalytic domain leads to the loss of function and subsequently elevated expression of pluripotency factors in breast cancer. The utilization of drug-likeness filters and molecular simulation has helped evaluate the pharmacological activity and binding abilities of selected drug candidates against the target proteins in many cancer studies. The current in silico study provides a pharmacoinformatic approach to decipher the potential of novel honokiol derivatives as therapeutic agents against breast cancer through binding of target LKB1 protein. Among the three honokiol derivatives, ligand-protein binding energy of 3' formylhonokiol with LKB1 protein was found to be the highest via molecular docking. Moreover, stability and compactness inferred for 3' formylhonokiol with LKB1 is suggestive of 3' formylhonokiol being an effective activator of LKB1 via simulation studies. It was further established that 3' formylhonokiol displays an excellent profile of distribution, metabolism, and absorption, indicating it as an anticipated future drug candidate.