Volume 93 Issue 2 | p. 25 | Concentrates
Issue Date: January 12, 2015

Sleep Aid Has Antituberculosis Activity

Ambien’s imidazo scaffold makes good starting point for finding novel antituberculosis agents
Department: Science & Technology
News Channels: Biological SCENE, Organic SCENE
Keywords: tuberculosis, medicinal chemistry

Zolpidem, better known as the sleep aid Ambien, is structurally similar to imidazo compounds that are promising antituberculosis agents. Marvin J. Miller of the University of Notre Dame and coworkers decided to see whether zolpidem also has anti-TB properties (ACS Infect. Dis. 2014, DOI: 10.1021/id500008t). Zolpidem itself is a mediocre inhibitor with, at best, a minimum inhibitory concentration (MIC) of 10 μM. But when the chemists rearranged the pieces of zolpidem into structural isomers, the MICs improved greatly, with one compound having an MIC of 0.004 μM. The researchers further elaborated the isomers into a series of analogs. In all, the team tested a total of 15 compounds against clinically relevant strains of drug-sensitive, multi-drug-resistant, and extensively drug-resistant Mycobacterium tuberculosis. Assays with a variety of microbes reveal that the compounds are selective for M. tuberculosis. So far, the compounds have been tested in cell lines but not in animal models. Studies to select optimal compounds are ongoing with scientists at Notre Dame, the pharmaceutical company Eli Lilly & Co., and the Infectious Disease Research Institute in Seattle, Miller says.

Chemical & Engineering News
ISSN 0009-2347
Copyright © American Chemical Society
Richard Cox (Thu Jan 15 18:20:20 EST 2015)
It would be appropriate to mention the contribution of Mr. Garrett Moraski, Dr. Miller's longtime collaborator, and Hsiri Therapeutics, the company working to commercialize those imidazopyridines developed at Notre Dame.
Richard Cox
Director, University of Notre Dame Office of Technology Transfer
Leave A Comment