Synthesis and antimicrobial activity of symmetrical two-tailed dendritic tricarboxylato amphiphiles

Antimicrobial activity of the water-soluble, dendritic tricarboxylato amphiphiles varies by microorganism as whether one or two tails or hydrophobicity or length predicts inhibition of growth. Two series of water-soluble, symmetrical two-tailed homologous dendritic amphiphiles—R 2NCONHC((CH 2) 2COOH) 3, 2( n, n), and R 2CHNHCONHC((CH 2) 2COOH) 3, 3( n, n), where R = n-C nH 2n+1—were synthesized and compared to R″NHCONHC((CH 2) 2COOH) 3, 1( n), R″ = n-C nH 2n+1, to determine whether antimicrobial activity was influenced by total or individual alkyl chain lengths, and whether antimicrobial activity depends on hydrophobicity or tail topology (one or two). In a broad screen of 11 microorganisms, 2( n, n) and 3( n, n) generally displayed higher minimal inhibitory concentrations (MICs) than 1( n) against growth as measured by broth microdilution assays. Chain-length specificity was observed against Candida albicans as 1( 16), 2( 8, 8), and 3( 8, 8) showed the lowest MIC in their respective series. The one case where two-tailed compounds displayed the lowest MICs— 3( 10, 10), 15 μM; 3( 11, 11), 7.2 μM; and 3( 12, 12), 6.9 μM—was against Cryptococcus neoformans.