Insights into mechanism of anticancer activity of pentacyclic oxindole alkaloids of Uncaria tomentosa by means of a computational reverse virtual screening and molecular docking approach

Alkaloid-rich extract from Uncaria tomentosa (cat's claw) has been reported to cause apoptosis in cancer lines. Oxindole pentacyclic alkaloids of the plant are responsible for this effect, yet their biological mechanism of action is not fully understood. In this work the set of these alkaloids underwent an extensive theoretical study with reverse virtual screening and molecular docking methods implemented in AutoDock, AutoDock Vina, and Molegro Virtual Docker. The results from these computational methods indicate that inhibition of several important targets including dihydrofolate reductase and mouse double minute 2 homolog (MDM2) may be responsible for the biological activity of the alkaloids. The docking results also show that the alkaloids can interact with Dvl-2, Akt-2, and leukotriene A4 hydrolase. Reverse virtual screening and molecular docking are valuable tools to aid identification of protein targets for bioactive hit molecules and could guide the design of in-depth biochemical activity tests and utilization of these alkaloids in anticancer drug development.