Next Article in Journal
Distinct Difference in Sensitivity of NIR vs. IR Bands of Melamine to Inter-Molecular Interactions with Impact on Analytical Spectroscopy Explained by Anharmonic Quantum Mechanical Study
Next Article in Special Issue
Inhibitory Antibodies Designed for Matrix Metalloproteinase Modulation
Previous Article in Journal
Tests on Material Compatibility of Phase Change Materials and Selected Plastics
Previous Article in Special Issue
High Consistency of Structure-Based Design and X-Ray Crystallography: Design, Synthesis, Kinetic Evaluation and Crystallographic Binding Mode Determination of Biphenyl-N-acyl-β-d-Glucopyranosylamines as Glycogen Phosphorylase Inhibitors
Article Menu
Issue 7 (April-1) cover image

Export Article

Open AccessArticle

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

1
Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China
2
School of life sciences and biological pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
3
Wuya College of innovation, Shenyang Pharmaceutical University, Shenyang 110016, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally.
Academic Editor: Rainer Riedl
Molecules 2019, 24(7), 1400; https://doi.org/10.3390/molecules24071400
Received: 18 March 2019 / Revised: 5 April 2019 / Accepted: 6 April 2019 / Published: 10 April 2019
(This article belongs to the Special Issue Drug Design)
  |  
PDF [2692 KB, uploaded 11 April 2019]
  |     |  

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 G1G13 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. View Full-Text
Keywords: monoamine oxidase A; prostate cancer; heptamethine cyanine dyes; isoniazid; molecular docking monoamine oxidase A; prostate cancer; heptamethine cyanine dyes; isoniazid; molecular docking
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Yang, X.-G.; Mou, Y.-H.; Wang, Y.-J.; Wang, J.; Li, Y.-Y.; Kong, R.-H.; Ding, M.; Wang, D.; Guo, C. Design, Synthesis, and Evaluation of Monoamine Oxidase A Inhibitors–Indocyanine Dyes Conjugates as Targeted Antitumor Agents. Molecules 2019, 24, 1400.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top