Characterization of VR118 quinacrine derivative as a potential anticancer agent

Abstract

The discovery and development of effective chemotherapeutic agents in the past few decades have immensely enhanced the treatment and management of human cancer. However, because these drugs are associated with adverse side effects, high genotoxicity, risk for secondary cancers and devastating effects on the patients’ immune system; the need for developing more effective anticancer agents remains. A priority Research shows that 9-aminoacridine (9AA) derivatives have substantial anticancer properties. The pharmacological properties of this agent are well characterized and this scaffold has been widely used to treat different diseases for decades. Quinacrine is a 9AA derivative, which was first discovered as an antimalarial compound in 1930’s and since then had been widely used in treating a variety of parasitic infections and demonstrated potential for cancer treatment. Importantly, the polypharmacology of Quinacrine makes it an attractive drug to treat a variety of cancers. Quinacrine acts by specifically targeting cellular signaling pathways that play an important role in cell survival. Given the distinctive cancer treating abilities of Quinacrine by specifically targeting cellular signaling pathways, it was the objective of this study to develop a compound that has similar properties as Quinacrine but has better efficacy and selectivity in targeting tumor cells. Therefore, for this project we created derivatives of 9AA compound using hybrid pharmapore approach and examined one of the derivatives of Quinacrine compound named VR118. After performing a series of experiments to test the efficacy and selectivity of the Quinacrine derivative VR118, I came to the conclusion that VR118 is highly effective in treating cancer cells and have the potential to selectively target cancer cells without causing severe harm to normal cells at concentrations applicable for malignant cell lines. This report discusses the efficacy and selectivity of VR118 compound in targeting cellular signaling pathways and the mechanisms through which VR118 kills cancer cells.