Iron transport-mediated drug delivery: practical syntheses and in vitro antibacterial studies of tris-catecholate siderophore-aminopenicillin conjugates reveals selectively potent antipseudomonal activity.
An artificial tris-catecolate siderophore with a tripodal backbone and its conjugates with ampicillin and amoxicillin were synthesized. Both conjugates exhibited significantly enhanced in vitro antibacterial activities against Gram-negative species compared to the parent drugs, especially against  Pseudomonas aeruginosa . The conjugates appeared to be assimilated by an induced bacterial iron transport process as their activities were inversely related to iron concentration. The easily synthesized tris-catecolate siderophore has great potential for future development of various drug conjugates to target antibiotic-resistant Gram-negative bacteria.
Department of Chemistry and Biochemistry, University of Notre Dame, 251 Nieuwland Science Hall, Notre Dame, Indiana 46556, USA.
Cheng
C
Ji
Patricia A
PA
Miller
Marvin J
MJ
Miller
D000658:Amoxicillin / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000667:Ampicillin / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001692:Biological Transport; D002396:Catechols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D060326:Chemistry Techniques, Synthetic; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy; D006801:Humans; D007501:Iron / Q000378:metabolism*; D011552:Pseudomonas Infections / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D017262:Siderophores / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D002396:Catechols; D017262:Siderophores; D000667:Ampicillin; D000658:Amoxicillin; D007501:Iron