Structure-activity relationships for antibacterial to antifungal conversion of kanamycin to amphiphilic analogues.
J Org Chem
; 80(9): 4398-411, 2015 May 01.
Article
em En
| MEDLINE
| ID: mdl-25826012
ABSTRACT
Novel fungicides are urgently needed. It was recently reported that the attachment of an octyl group at the O-4â³ position of kanamycin B converts this antibacterial aminoglycoside into a novel antifungal agent. To elucidate the structure-activity relationship (SAR) for this phenomenon, a lead compound FG03 with a hydroxyl group replacing the 3â³-NH2 group of kanamycin B was synthesized. FG03's antifungal activity and synthetic scheme inspired the synthesis of a library of kanamycin B analogues alkylated at various hydroxyl groups. SAR studies of the library revealed that for antifungal activity the O-4â³ position is the optimal site for attaching a linear alkyl chain and that the 3â³-NH2 and 6â³-OH groups of the kanamycin B parent molecule are not essential for antifungal activity. The discovery of lead compound, FG03, is an example of reviving clinically obsolete drugs like kanamycin by simple chemical modification and an alternative strategy for discovering novel antimicrobials.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tensoativos
/
Canamicina
/
Antibacterianos
/
Antifúngicos
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article