Design, synthesis and antitumor activities of thiazole-containing mitochondrial targeting agents.
Bioorg Chem
; 115: 105271, 2021 10.
Article
en En
| MEDLINE
| ID: mdl-34426155
ABSTRACT
In this study, a novel batch of thiazole-containing mitochondrial targeting agents were designed and synthesized. Four kinds of mitochondrial targeting moieties and six kinds of linkers were designed. Their structures were confirmed by NMR and HR-MS. The screening of antiproliferative activity revealed that most compounds displayed cytotoxicity on HeLa cancer cell. In particular, D1 has an IC50 value of 35.32 µmol·L-1 against HeLa cell. In addition, cellular respiratory activities were also tested on HeLa cancer cells. D1 had a basal oxygen consumption rate of 8.84 pmol·s-1·mL-1. Also, D1 inhibited the mitochondrial respiration of HeLa cell significantly at 5 µmol·L-1, as well as a complete inhibitory of oxygen consumption for cellular ATP coupling. Furthermore, the pKa, logP, and logD under different pH conditions of all the compounds were calculated by the ACD/Percepta-PhysChem Suite, and the results manifested the correlation between physicochemical properties and chemical activity of compounds. The results identify D1 as a promising mitochondria inhibitor and anticancer agent with appropriate physicochemical properties.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Tiazoles
/
Diseño de Fármacos
/
Mitocondrias
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Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
Bioorg Chem
Año:
2021
Tipo del documento:
Article