Influence of ring size in conformationally restricted ring I analogs of paromomycin on antiribosomal and antibacterial activity.
RSC Med Chem
; 12(9): 1585-1591, 2021 Sep 23.
Article
em En
| MEDLINE
| ID: mdl-34671740
ABSTRACT
In order to further investigate the importance of the conformation of the ring I side chain in aminoglycoside antibiotic binding to the ribosomal target several derivatives of paromomycin were designed with conformationally locked side chains. By changing the size of the appended ring between O-4' and C-6' used to restrict the motion of the side chain, the position of the C-6' hydroxy group was fine tuned to probe for the optimal conformation for inhibition of the ribosome. While the changes in orientation of the 6'-hydroxy group cannot be completely dissociated from the size and hydrophobicity of the conformation-restricting ring, overall, it is apparent that the preferred conformation of the ring I side chain for interaction with A1408 in the decoding A site of the bacterial ribosome is an ideal gt conformation, which results in the highest antimicrobial activity as well as increased selectivity for bacterial over eukaryotic ribosomes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
RSC Med Chem
Ano de publicação:
2021
Tipo de documento:
Article