Synthesis and evaluation of InhA inhibitors as potential antitubercular drugs

Charles University, Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Author: Simona Antalová Supervisor: doc. PharmDr. Mgr. Martin Krátký, Ph.D. Title of diploma thesis: Synthesis and evaluation of InhA inhibitors as potential antitubercular drugs Tuberculosis is an infectious disease that belongs to one of the top 10 causes of death worldwide. The most common cause of the disease are Mycobacterium tuberculosis complex strains. Antimicrobial therapy of the disease is nowadays complicated by alarming increase of strains resistant to standardly used antitubercular treatment. This is the reason of growing interest and significance in research of new potential antitubercular agents. One of the possible approaches is systematic modification of compounds with a known antimycobacterial activity, one of such compounds being triclosan. This substance acts as an uncompetitive inhibitor of enoyl-acyl-carrier protein reductase (InhA), an enzyme participating in the mycobacterial fatty acid biosynthesis pathway. It does not require activation by the mycobacterial KatG enzyme, thereby avoiding the most frequent mechanism of resistance to the frontline drug isoniazid targeting InhA too. The aim of the study was to synthesise ad evaluate new potential antitubercular drugs based..