Synthesis and Primary Activity Assay of Novel Benitrobenrazide and Benserazide Derivatives.
Molecules
; 29(3)2024 Jan 29.
Article
en En
| MEDLINE
| ID: mdl-38338374
ABSTRACT
Schiff bases attract research interest due to their applications in chemical synthesis and medicinal chemistry. In recent years, benitrobenrazide and benserazide containing imine moiety have been synthesized and characterized as promising inhibitors of hexokinase 2 (HK2), an enzyme overexpressed in most cancer cells. Benserazide and benitrobenrazide possess a common structural fragment, a 2,3,4-trihydroxybenzaldehyde moiety connected through a hydrazone or hydrazine linker acylated on an N' nitrogen atom by serine or a 4-nitrobenzoic acid fragment. To avoid the presence of a toxicophoric nitro group in the benitrobenrazide molecule, we introduced common pharmacophores such as 4-fluorophenyl or 4-aminophenyl substituents. Modification of benserazide requires the introduction of other endogenous amino acids instead of serine. Herein, we report the synthesis of benitrobenrazide and benserazide analogues and preliminary results of inhibitory activity against HK2 evoked by these structural changes. The derivatives contain a fluorine atom or amino group instead of a nitro group in BNB and exhibit the most potent inhibitory effects against HK2 at a concentration of 1 µM, with HK2 inhibition rates of 60% and 54%, respectively.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Benserazida
/
Aminoácidos
Idioma:
En
Revista:
Molecules
Asunto de la revista:
BIOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Polonia
Pais de publicación:
Suiza