Anti-leishmanial effect of spiro dihydroquinoline-oxindoles on volume regulation decrease and sterol biosynthesis of Leishmania braziliensis.
Exp Parasitol
; 198: 31-38, 2019 Mar.
Article
en En
| MEDLINE
| ID: mdl-30690024
ABSTRACT
Diverse spiro dihydroquinoline-oxindoles (JS series) were prepared using the BF3â¢OEt2-catalyzed imino Diels-Alder reaction between ketimine-isatin derivatives and trans-isoeugenol. Ten spiro-oxiindole derivatives were selected and evaluated at different stages of the life cycle of Leishmania braziliensis parasites, responsible for cutaneous leishmaniasis in South America. Among them, the 8'-ethyl-4'-(4-hydroxy-3-methoxyphenyl)-3'-methyl-3',4'-dihydro-1'H-spiro[indoline-3,2'-quinolin]-2-one called JS87 was able to inhibit the growth of promastigotes without affecting the mammalian cells viability, and to decrease the number of intracellular amastigotes of L. braziliensis. This spiro compound was found to act through the alteration of parasite internal regulation by disrupting the regulatory volume decrease (RVD), and to affect the sterol biosynthetic pathway at level of squalene epoxidase (SE) enzyme. These results revealed that the spiro annulation between quinoline and oxindole scaffolds enhances the anti-leishmanial activity, and could assist in the development of potent quinoline-oxindole hybrids against Leishmania braziliensis, the main etiological agent of cutaneous leishmaniasis in South America.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Quinolinas
/
Compuestos de Espiro
/
Leishmania braziliensis
/
Oxindoles
/
Antiprotozoarios
Límite:
Animals
País como asunto:
America do sul
/
Brasil
Idioma:
En
Año:
2019
Tipo del documento:
Article