Synthesis, antifungal activity and potential mechanism of fusidic acid derivatives possessing amino-terminal groups.
Future Med Chem
; 12(9): 763-774, 2020 05.
Article
em En
| MEDLINE
| ID: mdl-32208979
ABSTRACT
Aim:
Fusidic acid (FA) is a narrow-spectrum bacteriostatic antibiotic. We inadvertently discovered that a FA derivative modified by an amino-terminal group at the 3-OH position, namely 2, inhibited the growth of Cryptococcus neoformans. Methods &results:
Multiscale molecular modeling approaches were used to analyze the binding modes of 2 with eEF2. FA derivatives modified at the 3-OH position were designed based on in silico models; seven derivatives possessing different amino-terminal groups were synthesized and tested in vitro for antifungal activity against C. neoformans.Conclusion:
Compound 7 had the strongest minimum inhibitory concentration. Two protonated nitrogen atoms of 7 interacted with a negative electrostatic pocket of eEF2 likely explain the superiority of 7-2.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cryptococcus neoformans
/
Ácido Fusídico
/
Antifúngicos
Idioma:
En
Revista:
Future Med Chem
Ano de publicação:
2020
Tipo de documento:
Article