Synthesis, in vitro, and in silico studies of morpholine-based thiosemicarbazones as ectonucleotide pyrophosphatase/phosphodiesterase-1 and -3 inhibitors.
Int J Biol Macromol
; 266(Pt 2): 131068, 2024 May.
Article
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| MEDLINE
| ID: mdl-38531526
ABSTRACT
An extensive range of new biologically active morpholine based thiosemicarbazones derivatives 3a-r were synthesized, characterized by spectral techniques and evaluated as inhibitors of ENPP isozymes. Most of the novel thiosemicarbazones exhibit potent inhibition towards NPP1 and NPP3 isozymes. Compound 3â¯h was potent inhibitor of NPP1 with IC50 value of 0.55⯱â¯0.02. However, the most powerful inhibitor of NPP3 was 3e with an IC50 value of 0.24⯱â¯0.02. Furthermore, Lineweaver-Burk plot for compound 3â¯h against NPP1 and for compound 3e against NPP3 was devised through enzymes kinetics studies. Molecular docking and in silico studies was also done for analysis of interaction pattern of all newly synthesized compounds. The results were further validated by molecular dynamic (MD) simulation where the stability of conformational transformation of the best protein-ligand complex (3e) were justified on the basis of RMSD and RMSF analysis.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Pirofosfatasas
/
Tiosemicarbazonas
/
Morfolinas
/
Hidrolasas Diéster Fosfóricas
/
Simulación de Dinámica Molecular
/
Simulación del Acoplamiento Molecular
Límite:
Humans
Idioma:
En
Revista:
Int J Biol Macromol
Año:
2024
Tipo del documento:
Article
País de afiliación:
Pakistán