2. Academic Validation
  3. Novel salicylanilides from 4,5-dihalogenated salicylic acids: Synthesis, antimicrobial activity and cytotoxicity

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

  • Bioorg Med Chem. 2017 Feb 15;25(4):1524-1532. doi: 10.1016/j.bmc.2017.01.016.
Georgios Paraskevopoulos 1,  Sara Monteiro 2,  Rudolf Vosátka 3,  Martin Krátký 3,  Lucie Navrátilová 4,  František Trejtnar 4,  Jiřina Stolaříková 5,  Jarmila Vinšová 6
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Technology, Faculty of Pharmacy, Charles University in Prague, Heyrovského 1203, 50005 Hradec Králové, Czech Republic.
  • 2 Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 53210 Pardubice, Czech Republic.
  • 3 Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University in Prague, Heyrovského 1203, 50005 Hradec Králové, Czech Republic.
  • 4 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University in Prague, Heyrovského 1203, 50005 Hradec Králové, Czech Republic.
  • 5 Laboratory for Mycobacterial Diagnostics and Tuberculosis, Regional Institute of Public Health in Ostrava, Partyzánské náměstí 7, 70200 Ostrava, Czech Republic.
  • 6 Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University in Prague, Heyrovského 1203, 50005 Hradec Králové, Czech Republic. Electronic address: jarmila.vinsova@faf.cuni.cz.
PMID: 28126437 DOI: 10.1016/j.bmc.2017.01.016
Abstract

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=1-4μM), 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 0.5-4μM.

Keywords

Cytotoxicity; Double halogenation; In vitro antimycobacterial activity; Salicylanilides; Tuberculosis.

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