Structure-Activity Relationships of UTX-121 Derivatives for the Development of Novel Matrix Metalloproteinase-2/9 Inhibitors.
Chem Pharm Bull (Tokyo)
; 69(10): 1017-1028, 2021.
Article
em En
| MEDLINE
| ID: mdl-34602570
ABSTRACT
Celecoxib, a nonsteroidal anti-inflammatory drug, has been reported to have antitumor and antimetastatic activities, and it has potential for application in cancer treatments. The expression of matrix metalloproteinase (MMP)-2/9 is strongly correlated with cancer malignancy, and inhibition of these MMPs is believed to be effective in improving the antitumor and antimetastatic effects of drugs. We have previously revealed that UTX-121, which converted the sulfonamide of celecoxib to methyl ester, has more potent MMP-2/9 inhibitory activity than celecoxib. Based on these findings, we identified compounds with improved MMP inhibitory activity through a structure-activity relationship (SAR) study, using UTX-121 as a lead compound. Among them, compounds 9c and 10c, in which the methyl group of the p-tolyl group was substituted for Cl or F, showed significantly higher antitumor activity than UTX-121, and suppressed the expression of MMP-2/9 and activation of pro MMP-2. Our findings suggest that compounds 9c and 10c may be potent lead compounds for the development of more effective antitumor drugs targeting MMP.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Metaloproteinase 2 da Matriz
/
Metaloproteinase 9 da Matriz
/
Inibidores de Metaloproteinases de Matriz
/
Desenvolvimento de Medicamentos
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article