Design, Synthesis, and Evaluation of Monoamine Oxidase A Inhibitors⁻Indocyanine Dyes Conjugates as Targeted Antitumor Agents

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...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2019-04, Vol.24 (7), p.1400
Main Authors: Yang, Xiao-Guang, Mou, Yan-Hua, Wang, Yong-Jun, Wang, Jian, Li, Yan-Yu, Kong, Rui-Heng, Ding, Meng, Wang, Dun, Guo, Chun
Format: Article
Language:English
Subjects:
Accumulation
Amine oxidase (flavin-containing)
Antitumor activity
Binding sites
Conjugates
Cyanine dyes
Cytotoxicity
Deamination
Doxorubicin
Dyes
heptamethine cyanine dyes
Hypoxia
Inhibitors
Isoniazid
Metastases
Metastasis
Mitochondria
Molecular docking
monoamine oxidase A
Monoamines
Neurotransmitters
Older people
Prostate cancer
Tumor cells
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Summary: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 ⁻ 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 and showed potent anticancer activity with IC 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. , , and 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.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules24071400