In-Silico Assessments of Fruticulin-A and Demethylfruticulin-A Isolated from Salvia Species Against Important Anticancer Targets

Bioactive compounds derived from plants have been used to treat various ailments with minimal adverse effects 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.

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.

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.

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.