In-silico Prediction of Azadirachta indica Compounds as Potential Therapeutic Inhibitor of Lysyl Oxidase to Suppress Canine Mammary Tumor Proliferation

Abstract

Canine mammary tumor (CMT) is one of the leading causes of death in female dogs, mainly due to the unavailability/expensive treatment, adverse and untargeted nature of the contemporary therapeutics. Objectives: To discover a biological mediator from the Azadirachta indica extracts by targeting Lysyl Oxidase (LOX), which is one of the enzymes responsible for accelerating the development of tumors and altering cellular microenvironment in mammals is considered to be suitable targets for anti-cancerous drugs. Methods: Current study utilized computer-aided drug designing (CADD) to investigate 33 phytocompounds derived from this plant to check their potential inhibition properties against LOX protein. The phytochemicals were docked onto the protein and the ligands with the lowest binding energies were evaluated over the several parameters using PyRx software. Molecular dynamic simulation was also performed to further investigate the stability and conformational changes of the resultant ligand-protein complex by analyzing RMSD & RMSF values, H-bond graphs and Heat maps through VMD/NAMD softwares. Results: The results revealed that Azadirachtin to be the most pertinent agent in LOX inhibition with a docking score of -12.6 kcal/mol and showed promising in-silico stability as well. Drug likeliness potential was further assessed based on Lipinski’s rule of five which reflect the safer nature of this drug agent. Conclusions: Moreover, wet-lab in-vitro experiments followed by clinical trials are still needed to attest the validity of this virtually piloted phytocompound against LOX protein for CMT cure.