VII Simposio Internacional de Química 2019 "SIQ 2019" -VII Conferencia "Ciencias Químicas"

VII Simposio Internacional de Química 2019

SIQ 2019

IN VITRO EVALUATION OF ARYLSUBSTITUTED IMIDAZOLES AS ANTIPROTOZOAL AGENTS AND DOCKING STUDIES ON STEROL 14α-DEMETHYLASE (CYP51) FROM T. CRUZI, L. INFANTUM AND T. BRUCEI.

Resumen [ES]

There is an urgent need to discover and develop new drugs to combat parasitic diseases as Chagas disease (Trypanosoma cruzi), Sleeping sickness (Trypanosoma brucei) and Leishmaniasis (Leishmania ssp). These diseases are considered among the thirteen most unattended diseases worldwide according to the WHO. In the present work, the synthesis of 14 arylsubstituted imidazoles and its molecular docking onto sterol 14α-demethylase (CYP51) was executed. In addition, the compounds, antiprotozoal activity against T. brucei, T. cruzi, Tb. rhod and L.inf was evaluated. In vitro antiparasitic results of the arylsubstituted imidazoles against T. brucei, T. cruzi, Tb. rhod, L.inf indicated that all samples from arylsubstituted imidazole compounds presented interesting antiparasitic activity to various extent. The ligands 5a, 5c, 5e, 5f, 5g, 5i and 5j exhibited strong activity against T. brucei, T. cruzi, Tb. rhod and L.inf with IC50 values ranging from 0.88 to 4.98 μM. Most samples were cytotoxic against MRC-5 cell lines (1.17 < CC50 < 52.03 μM) and only ligand 5c showed a good selectivity against all tested parasites. According to the results of the molecular docking, the aromatic substituents in positions 1, 4 and 5 have mainly stabilizing hydrophobic interactions with the enzyme matrix, while the oxygen from NO2, SO3H and OH groups interacts with the Fe2+ ion of the Heme group.

Resumen [EN]

There is an urgent need to discover and develop new drugs to combat parasitic diseases as Chagas disease (Trypanosoma cruzi), Sleeping sickness (Trypanosoma brucei) and Leishmaniasis (Leishmania ssp). These diseases are considered among the thirteen most unattended diseases worldwide according to the WHO. In the present work, the synthesis of 14 arylsubstituted imidazoles and its molecular docking onto sterol 14α-demethylase (CYP51) was executed. In addition, the compounds, antiprotozoal activity against T. brucei, T. cruzi, Tb. rhod and L.inf was evaluated. In vitro antiparasitic results of the arylsubstituted imidazoles against T. brucei, T. cruzi, Tb. rhod, L.inf indicated that all samples from arylsubstituted imidazole compounds presented interesting antiparasitic activity to various extent. The ligands 5a, 5c, 5e, 5f, 5g, 5i and 5j exhibited strong activity against T. brucei, T. cruzi, Tb. rhod and L.inf with IC50 values ranging from 0.88 to 4.98 μM. Most samples were cytotoxic against MRC-5 cell lines (1.17 < CC50 < 52.03 μM) and only ligand 5c showed a good selectivity against all tested parasites. According to the results of the molecular docking, the aromatic substituents in positions 1, 4 and 5 have mainly stabilizing hydrophobic interactions with the enzyme matrix, while the oxygen from NO2, SO3H and OH groups interacts with the Fe2+ ion of the Heme group.

Sobre el ponente

Julio Rojas Vargas

MsC. Julio Rojas Vargas

UO Flag of Cuba
Información Práctica
English (US)
No definido
30 minutos
No definido
Autores
Phd América García López
MsC. Julio Rojas Vargas
Lic. Yulier Perez
Prof. Phd Matheus Froeyen
Prof. Phd Paul Cos
Palabras clave
arylsusbtituted imidazoles
in vitro evaluation
leishmania infantum
molecular docking
trypanosoma b. rhodesiense
trypanosoma brucei
trypanosoma cruzi