in-silico assessments of fruticulin-a and demethylfruticulin-a isolated from salvia species against important anticancer targets

Background and objectives: bioactive compounds derived from plants have been used to treat various ailments with minimal adverse effects. the in-silico methods are developed to predict the behavior of drug candidates before performing the in-vitro and in-vivo experiments. in the current study, a computational investigation was conducted to understand the probable mechanisms of two benzoquinone diterpenoids namely fruticulin-a and demethylfruticulin-a isolated from several salvia species by molecular docking and dynamic simulation approaches. methods: the above mentioned compounds with proven anticancer activity were docked against five selected target proteins that regulate cell proliferation and apoptosis including cyclin-dependent protein kinase 2 (cdk-2), cdk-6, dna topoisomerases i (topo i), topo ii and b-cell lymphoma-2 (bcl-2) using autodock 4.2. besides, molecular dynamics simulations were applied to evaluate the stability of the best-docked complexes. results: both compounds demonstrated remarkable binding affinity to cdk-2 than the known cdk-2 inhibitor. the trajectory analysis for 50 nanosecond (ns) revealed acceptable rmsd, rmsf and rg values during the entire molecular dynamic simulation which confirmed the stability of complexes. conclusion: the results of our study displayed that fruticulin-a and demethylfruticulin-a can be developed as excellent natural product derived cdk-2 inhibitors, and further biological experiments should be performed to confirm their use as an efficient option for treating cancer disease.