Gedunin Modification for Anticancer Properties Improvement against the Human NAD

Background: Cancer, also called malignancy, is an abnormal growth of cells. There are more than 100 types of cancer, including breast cancer, skin cancer, lung cancer, colon cancer, prostate cancer, and lymphoma. Symptoms vary depending on the type. Cancer treatment may include chemotherapy, radiation, and/or surgery. NAD + kinase (NADK) catalyzes the phosphorylation of nicotinamide adenine dinucleotide (NAD + ) to nicotinamide adenine dinucleotide phosphate (NADP + ) using ATP as the phosphate donor. NADP + is then reduced to NADPH by dehydrogenases, in particular glucose-6-phosphate dehydrogenase and the malic enzymes. NADPH functions as an important cofactor in a variety of metabolic and biosynthetic pathways. The demand for NADPH is particularly high in proliferating cancer cells, where it acts as a cofactor for the synthesis of nucleotides, proteins, and fatty acids. Materials and Methods: The Modification made to gedunin was done by substituting a CH3 group from the compound with NH2 using the marvin sketch software. The designed structural modifications were saved as mrv files which were then converted into SMILES strings for docking using the OpenBabel software. Molecular docking to predict the binding energy of gedunin and the modified analogue carried out using the AutoDock Vina software while pharmacokinetics parameters for each compound was predicted using the SwissADME server. Result: Following the modifications effected on gedunin, a positive result was observed as regarding the binding energies of the compounds. The NH2 analogue of gedunin exhibited a higher binding energy for the inhibition of the human NAD + kinase enzyme. Both compounds are predicted safe for administration as they both cannot permeate the blood brain barrier. Conclusion: Results from the molecular docking study showed that the NH2 analogue of gedunin might be a better anticancer agent. Laboratory synthesis and preclinical studies on the compound is therefore recommended.