Synthesis and optimisation of P3 substituted vinyl sulfone-based inhibitors as anti-trypanosomal agents.
Bioorg Med Chem
; 28(23): 115774, 2020 12 01.
Article
en En
| MEDLINE
| ID: mdl-32992251
ABSTRACT
A series of lysine-based vinyl sulfone peptidomimetics were synthesised and evaluated for anti-trypanosomal activity against bloodstream forms of T. brucei. This focused set of compounds, varying in the P3 position, were accessed in a divergent manner from a common intermediate (ammonium salt 8). Several P3 analogues exhibited sub-micromolar EC50 values, with thiourea 14, urea 15 and amide 21 representing the most potent anti-trypanosomal derivatives of the series. In order to establish an in vitro selectivity index the most active anti-trypanosomal compounds were also assessed for their impact on cell viability and cytotoxity effects in mammalian cells. Encouragingly, all compounds only reduced cellular metabolic activity in mammalian cells to a modest level and little, or no cytotoxicity, was observed with the series.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Sulfonas
/
Tripanocidas
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Irlanda