in silico study of analysing the capability of vinblastine and vincristine as inhibitory agents for targeting the cathepsin b enzyme by molecular docking

Background: cathepsin b (catb) is a lysosomal cysteine protease belonging to the papain family, involved in antigen processing during the immune response, hormone activation, and circulation, as well as in the pathology of chronic inflammatory diseases and cancer. the expression levels of the catb enzyme are elevated in numerous tumor cells, serving as both a prognostic and therapeutic marker for various cancers. considering the specific functional role of catb within cancer cells, it is possible to inhibit cancer progression by either reducing the activity of the catb proteolytic enzyme or enhancing lysosomal permeability. the alkaloids vincristine and vinblastine have been recognized for their significant contributions to the category of antitumor medications, owing to their strong anticancer effects, functioning as effective mitotic inhibitors. objectives: investigate the potential of vinblastine and vincristine molecules to function as ligands that interact with the catb enzyme through the process of molecular docking. methods: in this study, the first two ligands were sourced from the pubchem database. subsequently, the structure of the catb enzyme was acquired from the rcsb protein data bank website. after optimizing the molecular structures, they were saved in pdbqt format, which included the addition of gasteiger and kollman charges to both the ligands and the target enzyme, respectively. finally, the molecular docking process was carried out using the melligro virtual docker software, specifically targeting the cavity where the primary ligands bind to the catb enzyme. results: the results obtained from the molecular docking analysis demonstrated that vinblastine can bind to the active site of the catb enzyme, forming hydrogen bonds with met 196. the estimated bond length was 3.16 angstroms. the total energy measured was -218.647 kcal/mol for the moldock score and -129.661 kcal/mol for the rerank score. vincristine demonstrated significant potential for hydrogen bonding with the ser 175 residues of both chains a and b. the scores derived from the docking results suggest that vincristine possesses a relatively strong capacity to bind to this site, with a moldock score of -184.221 kcal/mol and a rerank score of -96.239 kcal/mol. additionally, the positioning of both ligands with the primary ligands of the cathepsin enzyme was compared using the discovery studio software. conclusions: both vincristine and vinblastine demonstrated considerable potential for interacting with the enzyme catb, which may facilitate additional research into the in vitro activity of these ligands.