Tris(1-alkylindol-3-yl)methylium salts as a novel class of antitumor agents

Abstract

Tris(1 alkylindol 3 yl)methanes were obtained and oxidized into tris(1 alkylindol 3 yl)methylium salts. The resulting salts are more toxic to cultured tumor cells than to non tumor ones. The cytotoxicity of tris(1 alkylindol 3 yl)methylium salts depends on the length of the substituent at the N atom of the heterocycle, increasing from an N unsubstituted derivative toward N butyl and N pentyl derivatives. A further increase in the length of the N alkyl substituent lowers the cytotoxicity. The cytotoxicity of tris(1 alkylindol 3 yl)methylium salts for tumor cells correlates with their antibacterial and antifungal activity. Tris(1 alkylindol 3 yl)methylium salts produced a cytocide effect on Gram positive microorganisms and the most active compounds, on Gram negative microorganisms as well. Similar patterns of the struc ture-activity relationship of N alkylated tris(indol 3 yl)methylium derivatives, which was ob served for various lines of tumor cells, bacteria, and fungi, suggest the general character of the mechanisms of the death of prokaryotic and eukaryotic cells induced by these compounds.

New opportunities for the synthesis of quinoxaline derivatives

“…The new quinoxaline transformation that we discovered is the result of a sequence of unit processes: competitive nucleophilic addition of the indole and the hydroxyl from water at the heterocyclic The discovered transformation of 6,7-difluoroquinoxalines in reactions with indoles lead to the synthesis of potentially biologically active compounds including derivatives of tris-indolylmethane homologs of Turbomycin A antibiotic [26].…”

“…Indole and derivatives thereof are widely used as heterocyclic C-nucleophiles in binding with various heterocyclic substrates [25]. The search for biologically active compounds among the indole derivatives is rather promising task since the indole ring acts as a constituent part of a series of important naturally occurring compounds like amino acids (tryptophan), neuromediator (serotonin) and antibiotic (Turbomycine A) [26].…”

N-(Hydroxyalkyl) Derivatives of tris(1H-indol-3-yl)methylium Salts as Promising Antibacterial Agents: Synthesis and Biological Evaluation

“…Recently, compounds containing triphenylmethyl or triindolylmethyl fragments have attracted the interest of researchers. This is due to the fact that some compounds of this type exhibit useful biological properties, such as antimicrobial and antiproliferative [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ].…”

“…Among them, a number of substances with a high (submicromolar) activity, even on multidrug-resistant strains of Staphylococcus aureus , were found. The first symmetrical alkyl derivatives we obtained were highly active against bacteria, but their toxicity was higher than the antibacterial activity [ 11 , 12 ]. Their structure needed to be improved.…”

The Mechanisms of Action of Triindolylmethane Derivatives on Lipid Membranes

“…The antibiotic turbomycin A, first isolated as a metabolic product of Saccharomyces cerevisiae, exhibits relatively low activity against Gram-positive bacteria [1] and presents a salt of tris(indol-3-yl)methylium [2]. Introduction of alkyl substituents at nitrogen atoms of the indole rings of the antibiotic was shown to significantly increase the antibacterial effect, expand the antibacterial spectrum, and induce the antitumor activity of the drug [3, 4].…”