Format

Send to

Choose Destination
Bioorg Med Chem Lett. 2017 Mar 1;27(5):1136-1140. doi: 10.1016/j.bmcl.2017.01.085. Epub 2017 Jan 31.

Selective inhibition of monoamine oxidase A by purpurin, an anthraquinone.

Author information

1
Department of Pharmacy and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Republic of Korea.
2
Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongju, Chungbuk 28116, Republic of Korea.
3
Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, Republic of Korea.
4
Department of Pharmacy and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Republic of Korea. Electronic address: hoon@sunchon.ac.kr.

Abstract

Monoamine oxidase (MAO) catalyzes the oxidation of monoamines that act as neurotransmitters. During a target-based screening of natural products using two isoforms of recombinant human MAO-A and MAO-B, purpurin (an anthraquinone derivative) was found to potently and selectively inhibit MAO-A, with an IC50 value of 2.50μM, and not to inhibit MAO-B. Alizarin (also an anthraquinone) inhibited MAO-A less potently with an IC50 value of 30.1μM. Furthermore, purpurin was a reversible and competitive inhibitor of MAO-A with a Ki value of 0.422μM. A comparison of their chemical structures suggested the 4-hydroxy group of purpurin might play an important role in its inhibition of MAO-A. Molecular docking simulation showed that the binding affinity of purpurin for MAO-A (-40.0kcal/mol) was higher than its affinity for MAO-B (-33.9kcal/mol), and that Ile 207 and Gly 443 of MAO-A were key residues for hydrogen bonding with purpurin. The findings of this study suggest purpurin is a potent, selective, reversible inhibitor of MAO-A, and that it be considered a new potential lead compound for development of novel reversible inhibitors of MAO-A (RIMAs).

KEYWORDS:

Competitive inhibitor; Molecular docking; Monoamine oxidase A; Purpurin; Selective inhibitor

PMID:
28188065
DOI:
10.1016/j.bmcl.2017.01.085
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center