Investigation of Anti-Cancer Properties of Novel Curcuminoids in Leukemic Cells and Dalton Lymphoma Ascites Model

Leukemia, one of the major causes of cancer death, ranks 11th worldwide among cancer-related deaths. The current treatment of leukemia faces challenges recently due to a high burden of side effects. It is well established that curcumin has anticancer and tumor-suppressing activities in several cancers in addition to leukemia. Accordingly, 15 derivatives were designed, prepared and evaluated for their cytotoxicity against the leukemic cell line MOLT-4, which led to the prioritization and further evaluation of compound 5i. Compared to curcumin, 5i was significantly more effective in inducing mitochondrial dysfunction in MOLT-4 cells; hence increased ROS production and cytotoxicity. Treatment groups showed translocation of mitochondrial membrane potential by flow cytometry analysis. Moreover, tumor volume reduction observed with 5i treatment in Dalton's Lymphoma model was with rather low toxicity signs. Intrinsic pathways of apoptosis were initiated by compound 5i that lowered Bcl-2 expression statically while augmenting cytochrome c levels both in vivo and in vitro. These results showcase the potent antiproliferative and cytotoxic effects of 5i at nanomolar doses against leukemia, at least 60X better than curcumin.