Abstract:

Depending on the use of multi-drug in therapy, microorganisms acquire resistance to drugs and existing therapeutics become insufficient. Fatty acid biosynthesis in microorganisms is essential for cell viability. Prokaryotic microorganism’s cells have different fatty acid synthesis mechanism than eukaryotic host cells. So this mechanism is a potential target for developing new antibiotic agents. Enoyl-ACP reductase enzyme is one of the important enzymes in bacterial fatty acid synthesis. Isoniazid shows the effect by inhibiting enoyl-ACP reductase enzyme. Mycolic acid is rich in cell wall of Mycobacterium tuberculosis and cell wall is highly impermeable. That makes microorganism more resistant to antibiotics and host cell defense mechanisms. By inhibiting this enzyme, mycolic acid synthesis, so cell wall synthesis can be stopped. In this study, inhibitors of enoyl-ACP reductase enzyme were analyzed by molecular docking methods and new molecules were designed. Efficiency of these molecules has been predicted via molecular modeling studies. u05, u06 and u07 make hydrogen bonds with Tyr158 and NAD+ cofactor which are responsible from the activity and they have less CDocker energies than known inhibitors. These three diphenyl ether derivatives were selected as lead compounds for further studies. In future works, synthesizing and determining activity on this enzyme are intended

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