Broad-spectrum antibacterial amphiphilic aminoglycosides: A new focus on the structure of the lipophilic groups extends the series of active dialkyl neamines

Cationic Amphiphiles Induce Macromolecule Denaturation and Organelle Decomposition in Pathogenic Yeast

“…The incidence of fungal infections has risen sharply in recent decades and the prevention and treatment of these infections relies on a very limited number of classes of antifungal drugs . Therefore, in recent years, several research groups, including ours, have been engaged in the study and development of membrane‐disrupting antifungal cationic amphiphiles based on the pseudo‐oligosaccharide structures of aminoglycoside (AG) antibiotics . The design of these antifungal agents is based on the attachment of hydrophobic residues to one or more positions of the AG scaffold.…”

Cationic Amphiphiles Induce Macromolecule Denaturation and Organelle Decomposition in Pathogenic Yeast

“…[10][11][12] Therefore,i nr ecent years,s everal research groups,i ncluding ours,h ave been engaged in the study and development of membrane-disrupting antifungal cationic amphiphiles based on the pseudo-oligosaccharide structures of aminoglycoside (AG) antibiotics. [13][14][15][16][17][18] The design of these antifungal agents is based on the attachment of hydrophobic residues to one or more positions of the AG scaffold. Like other non-peptide-based antimicrobial cationic amphiphiles,A G-derived cationic amphiphiles lack the peptide backbone of cationic antimicrobial peptides that is essential for the formation of plasma membrane pores.…”

Amphiphilic Aminoglycosides as Medicinal Agents

“…AAGs were synthesized by modification of the AG’s primary amine or hydroxyl functions. Lipophilic groups were conjugated to the AG’s core of NEO 1 (NEO), NEA 6 , PARO 2 , PARA 7 , KANA 3 and KANB 4 , TOB 5 and nebramine 8 (NEB) ( Figure 1 ) using several strategies [ 3 , 4 , 5 , 6 , 7 , 8 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. The amine functions of the selected AG were converted to alkyl- or aryl-amide(s) or to carbamates, leading to a decrease in the number of positive charges present at physiological pH.…”

“…The AAGs identified to be most active against Gram-positive and Gram-negative bacteria are mainly dialkyl and/or trialkyl derivatives of NEA 6 ( Figure 1 ), [ 5 , 34 , 35 ], of 1-methyl neosamine [ 36 ] and of NEB 8 , which were identified more recently and are briefly described [ 37 , 38 ]. In this part of the review, we summarize the main results obtained in the development of broad-spectrum antibacterial amphiphilic NEA 6 , PARA 7 and 1-methyl neosamine derivatives.…”

“…In the previous studies, the 3′,6-dinonyl NEA derivative 24 has been found to be the most active AAG against susceptible and resistant Gram-negative bacteria with the exception of resistant A. lwoffi (Al88–483). In the search for the best antibacterial amphiphilic NEA derivatives to develop further, different 3′,6- and 3′,4′-dialkyl NEAs having lipophilicity values close to that of 24 were synthesized and studied [ 35 ].…”