Synthesis, molecular docking and anti-mycobacterial evaluation of new imidazo[1,2-a]pyridine-2-carboxamide derivatives

Design, Synthesis, and Antimycobacterial Activity of Novel Theophylline‐7‐Acetic Acid Derivatives With Amino Acid Moieties

“…The favorable effect of aromatic substituents on the antimycobacterial activity has been observed in different purine‐related and non‐purine scaffolds . X‐ray data and docking studies with the target enzyme InhA, an enzyme essential for mycolic acid biosynthesis in M. tuberculosis show that two aromatic moieties connected by a short spacer is a suitable pharmacophore for enzyme inhibition.…”

“…GA allows one to select a subset of the most significant predictors using two evolutionary operations: random mutation and genetic recombination (crossover). The algorithm was used in the study with default values for the size of initial population (32), choice of parents (tournament selection), types of crossover (uniform crossover) and mutation (one-point mutation), and fitness function (Friedman's lack-of-fit scoring function with two parameters) (17). The selected variables were used in a stepwise linear regression, as implemented in the MDL QSAR v.2.2.…”

Design, synthesis, and biological evaluation of novel imidazo[1,2‐a]pyridinecarboxamides as potent anti‐tuberculosis agents

“…In addition, compound 16 showed acceptable PK properties, and further study is currently underway to improve its stability in liver microsome and hepatocyte. These compounds add to the growing list of imidazopyridine carboxamide derivatives that have been reported to possess anti-TB properties in the literature (Jose et al, 2015;Kang et al, 2014Kang et al, , 2017Moraski et al, 2011Moraski et al, , 2013Moraski et al, , 2015Pethe et al, 2013;Ramachandran et al, 2013;.…”

“…Another heterocyclic aromatic carboxamide, which has been extensively researched as a highly potent anti-TB scaffold, is the imidazopyridine-3-carboxamides (IPA) (Cheng, Moraski, Cramer, Miller, & Schorey, 2014;Jose et al, 2015;Kang et al, 2014Kang et al, , 2017Moraski et al, 2011Moraski et al, , 2013Moraski et al, , 2017Pethe et al, 2013). Using genome sequencing technique, it was established that IPA inhibitor family exert its anti-TB properties by targeting M. tuberculosis QcrB, an essential component of the electron transport chain (Abrahams et al, 2012).…”

Design, synthesis and anti-mycobacterial evaluation of imidazo[1,2-a]pyridine analogues

“…21 It also possesses a conserved active site and lacks apparent homologs in mammals. 28 A few reports mentioned above 21,26 also suggested the mode of action of antimycobacterial imidazopyridines through inhibition of InhA of MTB. Hence, based on the reported rationale, targeting the InhA enzyme followed by disruption of mycobacterial cellular homeostasis may be the most appropriate strategy for the current molecular docking study, and hence we docked our compounds at the active site of enoyl acyl carrier protein reductase from Mycobacterium tuberculosis (PDB 4TZK).…”