Development of Novel Isoindolone-Based Compounds against Trypanosoma brucei rhodesiense.
ChemistryOpen
; 10(9): 922-927, 2021 09.
Article
em En
| MEDLINE
| ID: mdl-34553828
ABSTRACT
This study identified the isoindolone ring as a scaffold for novel agents against Trypanosoma brucei rhodesiense and explored the structure-activity relationships of various aromatic ring substitutions. The compounds were evaluated in an integrated inâ
vitro screen. Eight compounds exhibited selective activity against T. b. rhodesiense (IC50 <2.2â
µm) with no detectable side activity against T. cruzi and Leishmania infantum. Compound 20 showed low nanomolar potency against T. b. rhodesiense (IC50 =40â
nm) and no toxicity against MRC-5 and PMM cell lines and may be regarded as a new lead template for agents against T. b. rhodesiense. The isoindolone-based compounds have the potential to progress into lead optimization in view of their highly selective inâ
vitro potency, absence of cytotoxicity and acceptable metabolic stability. However, the solubility of the compounds represents a limiting factor that should be addressed to improve the physicochemical properties that are required to proceed further in the development of inâ
vivo-active derivatives.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tripanossomicidas
/
Trypanosoma brucei rhodesiense
/
Isoindóis
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article