Target Based Approach For Synthesis And Evaluation Of Novel Anti Infective Molecules

Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains to be one of the causes of mortality and is the foremost reason from a sole bacterial infection besides HIV/AIDS. Totally Drug Resistant (TDR) strains, deadpan to the current line of treatment have emerged as there is no significant development in the discovery of new first-line drugs for the treatment of TB. After 40 years, recently, Johnson and Johnson s drug quotBedaquilinequot has been approved by US FDA to treat resistant TB cases. Current anti-tubercular drugs chiefly target cellular processes involved in bacterial growth and are either bacteriostatic or bactericidal. Therefore, there is a call for development of new antimycobacterial agents, possibly comprising new pharmacophore to provide effective therapy for emerging drug resistant tuberculosis. newlineThe present approach for this work is target-directed design and synthesis of molecules. Recent development in genetic analysis of mycobacterium has facilitated the understanding of basics of M. tuberculosis pathogenicity, identification of new drug targets vital for survival of tubercular bacilli. Hence, this work focuses on target-based design and synthesis of molecules as potential anti-infective agents for Mycobacterium tuberculosis with shikimate kinase as a target. newlineThe aromatic compounds such as aromatic amino acids, vitamin K and ubiquinone are important prerequisites for the metabolism of an organism. All organisms can synthesize these aromatic metabolites through shikimate pathway, except for mammals which are dependent on their diet for these compounds. Shikimic acid pathway or chorismate biosynthesis pathway operates as a link between carbohydrate metabolism and aromatic compounds biosynthesis. It is a metabolic pathway consisting of seven steps in which phosphoenolpyruvate and erythrose 4-phosphate from glycolysis and HMP shunt respectively are converted to chorismate. Many plants, parasites and bacteria utilize this chorismate for the synthesis of amino acids containing aromatic group