Structurally modified phthalimide derivatives were prepared through condensation of phthalic and tetrafluorophthalic anhydride with selected sulfonamides with variable yields. All compounds were screened for their antimycobacterium activity against Mycobacterium tuberculosis H37Ra (ATCC 25177) using a micro broth dilution technique. The fluorinated derivatives (compounds 2c, 2d, 2f and 2h) had antimycobacterium activity comparable with classical sulfonamide drugs. The minimum inhibitory concentration ( MIC) of compounds 2c, 2d, 2f and 2h was greater than that of isoniazid (MIC <0.02 mu g/mL) and in vitro activity was greater than that of pyrazinamide, another first line antimycobacterium drug (MIC 50-100 mu g/mL). The new compounds could be considered new lead compounds in the treatment of multi-drug resistant tuberculosis. (C) 2012 Elsevier Ltd. All rights reserved.