Background: Decaprenylphosphoryl-β-D-ribose epimerase (DprE1), a flavoprotein enzyme engaged in the biosynthesis of decaprenylphosphoryl-β-D-arabinofuranose (DPA), is the only contributor of arabinose residues which is fundamental for the mycobacterium cell wall constituents. DprE1 is an interesting target for antitubercular agent and has been
exploring to develop potential chemical entities as antitubercular agents.Objective:The objective of study is the development of novel antitubercular agents targeting Mtb Decaprenylphosphoryl-βD-ribose epimerase (DprE1).Methods:A series of isoxazole encompassed 1, 2, 4-triazoles were designed based on the antitubercular potential of triazoles and structural features of DprE1 inhibitors. Designed 1, 2, 4-triazoles were synthesized and characterized by spectral
studies. The in vitro anti-TB activity of the compounds was screened against Mycobacterium tuberculosis H37Rv strain.by
Microplate Almar Blue Assay and in vitro cytotoxicity against normal cell lines by MTT assay. Molecular docking study
was carried out on DprE1 enzyme to understand designed compounds interactions with amino acid residues at the active
site.Results:Antitubercular activity data revels that eight compounds (6d, 6e,7d, 7e, 10d, 10e, 11d and 11e) have shown promising antitubercular activity with minimum inhibitory concentration at 1.6µg/mL. Cytotoxicity data of anti-TB active compounds demonstrate the good safety profile on normal cell lines.Conclusion:Eight compounds have shown promising antitubercular activity with good safety profile on normal cell lines.
Molecular docking study ascertain that the synthesized compounds have shown non-covalent interactions with amino acid
residues of DprE1 enzyme.
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