Synthesis and antimicrobial evaluation of water-soluble, dendritic derivatives of epimeric 5alpha-cholestan-3-amines and 5alpha-cholestan-3-yl aminoethanoates.
To examine the effect of negatively charged steroidal amphiphiles on antimicrobial activity, two pairs of epimeric, dendritic tricarboxylato amphiphiles--4-(2-carboxyethyl)-4-[3-(5alpha-cholestan-3-yl)ureido]heptanedioic acid (1) and 4-(2-carboxyethyl)-4-[3-(5alpha-cholestan-3-yloxycarbonylmethyl)ureido]heptanedioic acid (2)--were synthesized. A broad antimicrobial screen of 11 microbes revealed that these amphiphiles only showed good activity against a methicillin-resistant isolate of Staphylococcus aureus (MRSA) and modest activity against an unrelated strain of S. aureus. The best activity, a minimal inhibitory concentration (MIC) of 27 microM, was found for the 3beta epimer of 1 against MRSA.
Sugandhi
Eko W
EW
Department of Chemistry MC 0212, Virginia Tech, Blacksburg, VA 24061, United States.
Slebodnick
Carla
C
Falkinham
Joseph O
JO
Gandour
Richard D
RD
D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D002778:Cholestanones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D008712:Methicillin / Q000494:pharmacology; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D008956:Models, Chemical; D015394:Molecular Structure; D012995:Solubility; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014867:Water
D000588:Amines; D000890:Anti-Infective Agents; D002778:Cholestanones; D014867:Water; C061920:cholestane-3,6-dione; D008712:Methicillin