Synthesis, biological evaluation and molecular docking studies of 6-(4-nitrophenoxy)-1H-imidazo[4,5-b]pyridine derivatives as novel antitubercular agents: future DprE1 inhibitors

Abstract

Tuberculosis is an air-borne disease, mostly affecting young adults in their productive years. Here, Ligand-based drug design approach yielded a series of 23 novel 6-(4-nitrophenoxy)-1H-imidazo[4,5-b]pyridine derivatives. The required building block of imidazopyridine was synthesized from commercially available 5,5-diaminopyridine-3-ol followed by four step sequence. Derivatives were prepared using various substituted aromatic aldehydes. All the synthesized analogues were characterized using NMR, Mass analysis and also screened for in vitro antitubercular activity against Mycobacterium tuberculosis (H37Rv). Four compounds, 5c (MIC-0.6 μmol/L); 5g (MIC-0.5 μmol/L); 5i (MIC-0.8 μmol/L); and 5u (MIC-0.7 μmol/L) were identified as potent analogues. Drug receptor interactions were studied with the help of ligand docking using maestro molecular modeling interphase, Schrodinger. Here, computational studies showed promising interaction with other residues with good score, which is novel finding than previously reported. So, these compounds may exhibit in vivo DprE1 inhibitory activity. Electronic supplementary materialThe online version of this article (10.1186/s13065-018-0515-1) contains supplementary material, which is available to authorized users.

3D QSAR Pharmacophore Based Virtual Screening, ADME Analysis and Estimation of MM/GBSA binding Free Energies of Azoles as a Potential Inhibitor of DprE1 for Mycobacterium Tuberculosis

“…The previous studies suggest that some of the molecules such as benzthiazinones against DprE1 have antibacterial activity without exhibiting TB resistance [17]. This indirectly con rms that enzyme DprE1 is a promising drug target to design new anti-TB drugs [18][19][20][21][22].…”

Imidazo[4,5-b]Pyridines: From Kinase Inhibitors to more Diversified Biological Properties

“…Tuberculosis, known for a long time to be a major cause of morbidity and mortality throughout the world, has for several decades been a neglected disease in both industrialized and developing countries [82]. Gawad and Bonde [83] reported the synthesis of new compounds screened for in vitro antitubercular activity against the pathogen Mycobacterium tuberculosis (H37Rv). Four compounds (Fig.…”