Guanidinium rich dendron-appended hydnocarpin exhibits superior anti-neoplastic effects through caspase mediated apoptosis

Abstract

Medicinal plants have truly demonstrated their potential as a repository of active biomolecules with promising therapeutic potential and represent an important source for the identification of novel drug leads. Hydnocarpus wightiana Blume is a well known medicinal plant and the acetone extract of its seed demonstrated superior free radical scavenging properties with a high total phenolic and flavonoid content. Hydnocarpin (Hy), which has been isolated and purified from the acetone extract, promotes moderate cytotoxicity in cancer cells. In an attempt to increase the efficiency of Hy as an anticancer agent, chemical coupling with a highly efficient, non-toxic cell-penetrating guanidinium-rich poly(propylene imine) dendron (G8) was attempted. The resultant modified construct (Hy–G8) exhibits superior cytotoxicity preferentially on cancer cells through the induction of apoptosis mediated by caspases. The hybrid construct was also found to be a promising anti-metastatic agent. Therefore, Hy–G8 functioned primarily as a hit compound which requires extensive interdisciplinary approaches and legitimate engineering to accomplish a futuristic lead candidate in cancer chemotherapy.