Campus Units

Chemistry, Physics and Astronomy, Biomedical Sciences

Document Type

Article

Publication Version

Published Version

Publication Date

4-2017

Journal or Book Title

International Journal for Parasitology: Drugs and Drug Resistance

Volume

7

Issue

1

First Page

12

Last Page

22

DOI

10.1016/j.ijpddr.2016.12.001

Abstract

Nematode parasites infect ∼2 billion people world-wide. Infections are treated and prevented by anthelmintic drugs, some of which act on nicotinic acetylcholine receptors (nAChRs). There is an unmet need for novel therapeutic agents because of concerns about the development of resistance. We have selected Asu-ACR-16 from a significant nematode parasite genus, Ascaris suum, as a pharmaceutical target and nicotine as our basic moiety (EC50 6.21 ± 0.56 μM, Imax 82.39 ± 2.52%) to facilitate the development of more effective anthelmintics.

We expressed Asu-ACR-16 in Xenopus oocytes and used two-electrode voltage clamp electrophysiology to determine agonist concentration-current-response relationships and determine the potencies (EC50s) of the agonists.

Here, we describe the synthesis of a novel agonist, (S)-5-ethynyl-anabasine, and show that it is more potent (EC50 0.14 ± 0.01 μM) than other nicotine alkaloids on Asu-ACR-16. Agonists acting on ACR-16 receptors have the potential to circumvent drug resistance to anthelmintics, like levamisole, that do not act on the ACR-16 receptors.

Comments

This article is published as Zheng, Fudan, Xiangwei Du, Tsung-Han Chou, Alan P. Robertson, W. Yu Edward, Brett VanVeller, and Richard J. Martin. "(S)-5-ethynyl-anabasine, a novel compound, is a more potent agonist than other nicotine alkaloids on the nematode Asu-ACR-16 receptor." International Journal for Parasitology: Drugs and Drug Resistance 7, no. 1 (2017): 12-22. DOI: 10.1016/j.ijpddr.2016.12.001. Posted with permission.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Copyright Owner

The Author(s)

Language

en

File Format

application/pdf

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