Schiff bases of indoline-2,3-dione (isatin) derivatives as efficient agents against resistant strains of Mycobacterium tuberculosis

A library of 143 Schiff bases of isatin derivatives was evaluated for its activity against the different types ofMycobacterium tuberculosis. Ten of the tested derivatives showed promising activity against the wild-type strain with MIC values range between 10-0.156 µg/mL. The most active derivatives (A2, A6, D5 and D8) were further tested against a panel of six single resistant Mycobacterium tuberculosisstrains. The results revealedinteresting results regarding derivative D8 which showed enhanced activity against the Streptomycin resistant strain. Further investigations showed D8 to have equipotent activity to INH against rifampin-resistant strains as well as being 4 times more active than rifampin against the ofloxacin-resistant strains. A pharmacophore modeling study was conducted to determine critical molecular components for activity and to provide insights towards further optimization. This work was presented at the 246th American Chemical Society meeting, Indianapolis, Indiana -USA, September 8-14, 2013