Toxicity and antimicrobial activity of tropylated aniline and its derivatives

Abstract

This study investigated the biological activity of tropylated aniline 4-(7-cyclohepta-1,3,5-trienyl)aniline and its derivatives belonging to the group of secondary aromatic amines – N-2-hydroxyphenylmethyl-4¹-(7-cyclohepta-1,3,5-trienyl)aniline and the group of azomethines – N-2-hydroxyphenylmethylene-4¹-(7-cyclohepta-1,3,5-trienyl)aniline. Tropylated aniline was synthesized by mixing tropyllium tetrafluoroborate and aniline in ethanol. N-2-hydroxyphenylmethyl-4¹-(7-cyclohepta-1,3,5-trienyl)aniline and N-2-hydroxyphenylmethylene-4¹-(7-cyclohepta-1,3,5-trienyl)aniline were obtained via a one-pot multicomponent synthesis. Tropylated aniline and its derivatives showed no toxic effects on Galleria mellonella larvae upon invasive administration of 10 µL solutions at a concentration of 1 mg/mL (10 µg/larva). In vitro experiments demonstrated that Gram-negative bacteria and Gram-positive bacteria with hydrophilic cell walls exhibit low susceptibility to tropylated aniline and are resistant to its derivatives. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the studied compounds were determined. The MBC/MIC ratio for all susceptible bacteria was ≤4, indicating their bactericidal activity. A dependence of bacterial susceptibility to tropylated aniline and its derivatives on the level of bacterial cell hydrophobicity was demonstrated. High susceptibility to the studied compounds was revealed in mycomembrane bacteria of the Mycobacterium genus, whose cell walls contain mycolic acids and exhibit a high level of hydrophobicity. The obtained compounds are of practical relevance as potential anti-tuberculosis agents.

Key words: antibacterial activity, hydrophobicity, tropylidene cycle, mycomembrane, toxicity, Galleria mellonella