Executive Summary : | Metabolic reprogramming is a key factor in cell proliferation and cancer, requiring a calibrated upregulation of glycolysis, also known as the Warburg effect. Tumors rely on optimal oxidative phosphorylation for biosynthesis and energy demands, and any deviation from these metabolic events can lead to cell death. This project proposes a set of carefully designed molecules to interrogate metabolic reprogramming and develop small molecules that selectively alter oxidative phosphorylation in rapidly dividing cancer cells. The focus is expected to reduce off-target pharmacological action and achieve stage-wise inhibition of glycolysis processes. Small molecule scaffolds will be designed to probe the energy metabolism of HeLa cells, including their possible mitochondrial localization and distribution. Targeted depletion of glycolytic reserve would result in catastrophic energy deprivation for rapidly proliferating cells. The study will also study cancer cell biomechanics using atomic force microscopy, determining Young's modulus through Hertz model fitted force-distance curves. A decrease in AFM-determined cell stiffness may exhibit inhibition of cell motility and metastasis. |