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

Two series of water-soluble, symmetrical two-tailed homologous dendritic amphiphiles—R2NCONHC((CH2)2COOH)3, 2(n,n), and R2CHNHCONHC((CH2)2COOH)3, 3(n,n), where R = n-CnH2n+1—were synthesized and compared to R″NHCONHC((CH2)2COOH)3, 1(n), R″ = n-CnH2n+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.

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.Figure optionsDownload as PowerPoint slide