Synthesis and antimicrobial activity of symmetrical two-tailed dendritic tricarboxylato amphiphiles.
Two series of water-soluble, symmetrical two-tailed homologous dendritic amphiphiles--R(2)NCONHC((CH(2))(2)COOH)(3), 2(n,n), and R(2)CHNHCONHC((CH(2))(2)COOH)(3), 3(n,n), where R=n-C(n)H(2n+1)--were synthesized and compared to R''NHCONHC((CH(2))(2)COOH)(3), 1(n), R''=n-C(n)H(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 microM; 3(11,11), 7.2microM; and 3(12,12), 6.9 microM-was against Cryptococcus neoformans.
Sugandhi
Eko W
EW
Department of Chemistry MC 0212, Virginia Tech, Blacksburg, VA 24061, USA.
Falkinham
Joseph O
JO
Gandour
Richard D
RD
D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects*; D003455:Cryptococcus neoformans / Q000187:drug effects*; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D057927:Hydrophobic and Hydrophilic Interactions; D012995:Solubility; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry
D000935:Antifungal Agents; D050091:Dendrimers; D014867:Water