Cancer remained one of the leading causes of mortality with 10 million deaths in 2020. The most widely used treatment modality is chemotherapy using platinum drugs. However, chemo-resistance in cancer cells and dose-limiting toxic side effects severely limit the efficacy of platinum-based therapy. We are working towards designing new anticancer agents to tackle the issues with current chemotherapeutic drugs. We recently identified a few small molecule HITs which exert anticancer activity through novel mechanism of action and have the potential to overcome chemo-resistance. Importantly, these agents showed excellent tumor inhibition properties in animal model. In the colloquium, I will discuss the design principle, synthesis and biological evaluation of these new class of chemotherapeutics.