Design, Synthesis, and Evaluation of Monoamine Oxidase A Inhibitorsâ»Indocyanine Dyes Conjugates as Targeted Antitumor Agents.
Molecules
; 24(7)2019 Apr 10.
Article
em En
| MEDLINE
| ID: mdl-30974737
ABSTRACT
Monoamine oxidase A (MAOA) is an important mitochondria-bound enzyme that catalyzes the oxidative deamination of monoamine neurotransmitters. Accumulating evidence suggests a significant association of increased MAOA expression and advanced high-grade prostate cancer (PCa) progression and metastasis. Herein, a series of novel conjugates combining the MAOA inhibitor isoniazid (INH) and tumor-targeting near-infrared (NIR) heptamethine cyanine dyes were designed and synthesized. The synthesized compounds G1â»G13 were evaluated in vitro for their cytotoxicity against PC-3 cells using the MTT assay, and molecular docking studies were performed. Results showed that most tested compounds exhibited improved antitumor efficacy compared with INH. Moreover, conjugates G10 and G11 showed potent anticancer activity with IC50 values (0.85 and 0.4 µM respectively) comparable to that of doxorubicin (DOX). This may be attributable to the preferential accumulation of these conjugates in tumor cells. G10, G11, and G12 also demonstrated moderate MAOA inhibitory activities. This result and the results of molecular docking studies were consistent with their cytotoxicity activities. Taken together, these data suggest that a combination of the MAOA inhibitor INH with tumor-targeting heptamethine cyanine dyes may prove to be a highly promising tool for the treatment of advanced prostate cancer.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
/
Carbocianinas
/
Simulação de Acoplamento Molecular
/
Corantes Fluorescentes
/
Isoniazida
/
Monoaminoxidase
/
Inibidores da Monoaminoxidase
/
Proteínas de Neoplasias
Limite:
Humans
/
Male
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article