Novel salicylanilides from 4,5-dihalogenated salicylic acids: Synthesis, antimicrobial activity and cytotoxicity

Publication date: Available online 14 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Georgios Paraskevopoulos, Sara Monteiro, Rudolf Vosátka, Martin Krátký, Lucie Navrátilová, František Trejtnar, Jiřina Stolaříková, Jarmila Vinšová
Salicylanilides have proved their activity against tuberculosis (TB). One weak electron-withdrawing substituent is favored at the salicylic part, specially Cl or Br atoms at positions 4 or 5. On the other hand, the antimycobacterial activity of salicylanilides is negatively affected when a strong electron-withdrawing substituent (-NO2) is present at the same positions. Herein we describe the synthesis and characterization of novel salicylanilides possessing two weak electron-withdrawing groups (halogen atoms) at their salicylic part and compare their antitubercular activity with their monohalogenated analogues. All dihalogenated derivatives proved to possess antitubercular activity at a very narrow micromolar range (MIC= 1-4 μM), similar with their most active monohalogenated analogues. More importantly, the most active final molecules were further screened against multidrug resistant strains and found to inhibit their growth at the range of 0.5-4 μM.

Graphical abstract

http://ift.tt/2jiBZGd