Virtual Screening and in vitro Antibacterial Activity for the Identification of Novel Inhibitors of Mycobacterium tuberculosis Methionine Aminopeptidase

Background: With the increase of resistance rates among many pathogenic bacterial species, this led to a huge public health problem; the ongoing need for the development of new antibiotics that target new pathways is obvious. As such, the MetAP is an attractive target for the development of new antimicrobials, because it is involved in the protein processing in bacteria. Objective: To screen the potential MetAP of Mycobacterium tuberculosis inhibitor by in silico virtual screening of ZINC database and evaluate the best potential lead molecule by in vitro studies. Results and Conclusion: In this research, we used the FlexX program to screen collections of chemical compounds against the protein target. Before performing the molecular docking, FlexX was validated by tow tests to determine the reproducibility of docking program. After the virtual screening, nine chemical compounds of the top hits predicted were purchased and evaluated in vitro for their antibacterial activities against Mycobacterium smegmatis, using the paper disc diffusion method. Among the studied compounds, only the compound ZINC04785369 inhibited the bacterial growth and could be promising antimycobacterial agents. All these may provide something useful for the development of the potent inhibitors.