Synthesis, antiproliferative and antiplasmodial evaluation of new chloroquine and mefloquine-based harmiquins.
Acta Pharm
; 73(4): 537-558, 2023 Dec 01.
Article
en En
| MEDLINE
| ID: mdl-38147482
ABSTRACT
Here we present the synthesis and evaluation of the biological activity of new hybrid compounds, ureido-type (UT) harmiquins, based on chloroquine (CQ) or mefloquine (MQ) scaffolds and ß-carboline alkaloid harmine against cancer cell lines and Plasmodium falciparum. The hybrids were prepared from the corresponding amines by 1,1'-carbonyldiimidazole (CDI)-mediated synthesis. In vitro evaluation of the biological activity of the title compounds revealed two hit compounds. Testing of the antiproliferative activity of the new UT harmiquins, and previously prepared triazole-(TT) and amide-type (AT) CQ-based harmiquins, against a panel of human cell lines, revealed TT harmiquine 16 as the most promising compound, as it showed pronounced and selective activity against the tumor cell line HepG2 (IC 50 = 5.48 ± 3.35 µmol L-1). Screening of the antiplasmodial activities of UT harmiquins against erythrocytic stages of the Plasmodium life cycle identified CQ-based UT harmiquine 12 as a novel antiplasmodial hit because it displayed low IC 50 values in the submicromolar range against CQ-sensitive and resistant strains (IC 50 0.06 ± 0.01, and 0.19 ± 0.02 µmol L-1, respectively), and exhibited high selectivity against Plasmodium, compared to mammalian cells (SI = 92).
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Mefloquina
/
Cloroquina
/
Antimaláricos
Límite:
Humans
Idioma:
En
Revista:
Acta Pharm
Asunto de la revista:
FARMACIA
/
FARMACOLOGIA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Croacia
Pais de publicación:
Polonia