Abstract:
:The re-emergence of tuberculosis (TB) as a global health problem over the past few decades, accompanied by the rise of drug-resistant strains of Mycobacterium tuberculosis, emphasizes the need for discovery of new therapeutic drugs against this disease. The emerging serious problem both in terms of TB control and clinical management prompted us to synthesize a novel series of heterocyclic o/m/p substituted diphenyl ether derivatives and determine their activity against H37Rv strain of Mycobacterium. All 10 compounds inhibited the growth of the H37Rv strain of mycobacterium at concentrations as low as 1 microg/mL. This level of activity was found comparable to the reference drugs rifampicin and isoniazid at the same concentration. Molecular modeling of the binding of the diphenyl ether derivatives on enoyl-ACP reductase, the molecular target site of triclosan, indicated that these compounds fit within the binding domain occupied by triclosan. Hence the diphenyl ether derivatives tested in this study were docked to ENR and the binding of the diphenyl ether derivatives was also estimated using a variety of scoring functions that have been compiled into the single consensus score. As the scores ranged from 47.27% to 65.81%, these bioactive compounds appear to have a novel mechanism of action against M. tuberculosis, and their structural features should be studied further for their potential use as new antitubercular drugs.
journal_name
Eur J Med Chemjournal_title
European journal of medicinal chemistryauthors
Kini SG,Bhat AR,Bryant B,Williamson JS,Dayan FEdoi
10.1016/j.ejmech.2008.04.013subject
Has Abstractpub_date
2009-02-01 00:00:00pages
492-500issue
2eissn
0223-5234issn
1768-3254pii
S0223-5234(08)00203-1journal_volume
44pub_type
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