Synthesis and Immunosuppressive Activity of New Mycophenolic Acid Derivatives.
Med Chem
; 13(2): 159-167, 2017.
Article
em En
| MEDLINE
| ID: mdl-27924728
ABSTRACT
BACKGROUND:
Immunosuppressive drugs are widely used to prevent and treat allograft rejection and autoimmune diseases. Mycophenolic acid (MPA) and its derivatives are currently one of the most prescribed immunosuppressive drugs; however, metabolic drawbacks and variable interand intrapatient responses limit their use.OBJECTIVE:
In order to find out new safe and effective immunosuppressive compounds, we report here the synthesis and pharmacological evaluation of hybrid MPA derivatives containing the thalidomide/ phthalimide subunits.RESULTS:
All compounds 3a-d exhibited an enhanced ability to reduce the levels of pro-inflammatory cytokines compared to the parental drugs MPA and thalidomide. The mixed lymphocyte reaction assay has demonstrated that compound 3d - (E)-(3-(1,3-dioxoisoindolin-2-yl)-2,6-dioxopiperidin-1- yl)methyl-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4- enoate - has superior activity compared to that of MPA. In addition, compound 3d was less cytotoxic against Jurkat cells than MPA and did not demonstrate in vivo genotoxic effect.CONCLUSION:
All these data have shown that compound 3d is a promising lead compound useful in the immunosuppressive therapy.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Imunossupressores
/
Ácido Micofenólico
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Med Chem
Ano de publicação:
2017
Tipo de documento:
Article