COMPOUNDS BASED ON TRIS(1-ALKYLINDOL-3-YL)METHAN FOR OVERCOMING DRUG RESISTANCE IN PATHOGENS

Abstract

Trls(1-alkylindol-3-yl)methylium salts that are trls(1-alkylindol-3-yl)methan derivatives with high antibacterial and antifungal activity were obtained through chemical synthesis. These salts were practically not inferior to levolloxacin in their activity against Grampositive bacteria and were almost as good as amphotericin B against yeast Candida albicans yeast or Aspergillus niger fungi. Several derivatives demonstrated moderate activity against Gram-negative bacteria. Antimicrobial activity of derivatives depended primarily on the length of their alkyl radicals, was maximal when radicals had four - five carbon atoms and practically did not practically depend on radical branching. Tris(1-alkylindol-3-yl)methan derivatives revealed an extremely high activity (MIC 0.13-1.0 ^g/ml) against bacteria that are sensitive to antibiotics and resistant strains, including multidrug-resistant clinical isolates. The most active compounds showed activity in vivo in staphylococcal and candida sepsis models in mice. These results testify to the prospects of the development of new drugs on the basis of tris(1-alkylindol-3-yl)methan capable to overcome drug resistance in pathogens.

Keywords

• antibacterial and antifungal antibiotics
• tris(1-alkylindol-3-yl)methan derivatives
• tris(1-alkylindol-3-yl)methylium salts
• turbomycin a analogues
• antimicrobial activity in vitro and in vivo
• multi drug resistance
• staphylococcal and candida sepsis models in mice