Novel derivatives of nitro-substituted salicylic acids: Synthesis, antimicrobial activity and cytotoxicity
Abstrakt
Inspired by the high antituberculous activity of novel nitro-substituted derivatives and based on promising predicted ADMET properties we have synthesized a series of 33 salicylanilides containing nitro-group in their salicylic part and evaluated them for their in vitro antimycobacterial, antimicrobial and antifungal activities. The presence of nitro-group in position 4 of the salicylic acid was found to be beneficial and the resulting molecules exhibited minimum inhibitory concentrations (MICs) ranging from 2 to 32 mu M against Mycobacterium tuberculosis.
The best activity was found for 2-hydroxy-4-nitro-N-[4-(trifluoromethyl)phenyl] benzamide (MIC = 2 mu M). 4-Nitrosalicylanilides were also found to be active against all Staphylococcus species tested while for MRSA strain 2-hydroxy-4-nitro-N-[4-(trifluoromethyl)phenyl] benzamide's MIC was 0.98 mu M. None of the nitrosalicylanilides was active against Enterococcus sp.
J 14365/08 and no considerable activity was found against Gram-negative bacteria or fungi. The hepatotoxicity of all nitrosalicylanilides was found to be in the range of their MICs for HepG2 cells.