Discovery of Novel Pyruvate Kinase Inhibitors Against

objectivesLeishmaniasis is one of the common forms of neglected parasitic diseases that cause a worldwide disease burden without any effective therapeutic strategy. Control of the disease currently relies on chemotherapy because most of the available drugs have toxic side-effects and drug-resistant strains have emerged. Therefore, the development of new therapeutic strategies to treat patients for leishmaniasis has become a priority. The first step in drug discovery is to identify an effective drug target by methods such as system biology. Protein kinases are a promising drug target for different diseases. Due to lack of a functional krebs cycle in MATERIALS AND

methodsThis study sought to discover FDA approved compounds against the leishmanial pyruvate kinase protein. Our approach involved using quantitative proteomics, protein interaction networks and docking to detect new drug targets and potent inhibitors.

resultsPyruvate kinase was determined as the potential drug target based on protein network analysis. The docking studies suggested trametinib and irinotecan with high binding energies of -10.4 and -10.3 kcal/mol, respectively, as the potential chemotherapeutic agents against

conclusionThis study demonstrated the importance of integrating protein network analysis and molecular docking to identify new anti-leishmanial drugs. These potential inhibitors constitute novel drug candidates that should be tested