中国365bet中文官网

Note to journalists: Please report that this research will be presented at a meeting of the American Chemical 中国365bet中文官网.

A press conference on this topic will be held Wednesday, Aug. 19, at 1 p.m. Eastern time online at http://www.acs.org/fall2020pressconferences.

WASHINGTON, Aug. 17, 2020 鈥� At 11 million cases annually, urinary tract infections (UTIs) are the most common outpatient infections in the U.S., according to the U.S. Department of Health and Human Services. At least half of all women will have a UTI during their lifetimes, and many of the infections 鈥� which have increasingly become resistant to a wide array of antibiotics 鈥� recur. Now, researchers report early progress toward developing a new class of antibiotics that would fight these infections by starving the causative bacteria of iron.

The researchers will present their results today at the American Chemical 中国365bet中文官网 (ACS) Fall 2020 Virtual Meeting & Expo. ACS is holding the meeting through Thursday. It features more than 6,000 presentations on a wide range of science topics.

鈥淵ou can鈥檛 stop bacteria from evolving and developing resistance to antibiotics,鈥� says Mary Rose Ronquillo, an undergraduate student who works in the lab of Scott C. Eagon, Ph.D. 鈥淭he aim of our research is to develop a drug that acts in a different way from current drugs 鈥� by depriving the bacteria of iron, a key nutrient essential to their survival.鈥�

Currently, most drugs that treat UTIs caused by uropathogenic E. coli (UPEC) either disrupt synthesis of the bacterial cell wall or interfere with bacterial DNA replication. Since the urinary tract is an iron-deficient environment, UPEC have evolved several ways to obtain iron, such as by producing molecules called siderophores that sop up iron bound to host proteins.

The researchers, who are at California Polytechnic State University, have collaborated on this project with other scientists at the University of Michigan School of Medicine. The collaborators previously showed that the iron acquisition process can be a target for small molecules for possible UTI treatment. In that study, they screened nearly 150,000 compounds and identified 16 that stop these bacteria from growing under iron-limiting conditions. Of these 16, two compounds were linked to disruption of the bacterial TonB system, which consists of three transmembrane proteins that help UPEC take up iron. Eagon鈥檚 group is focusing on these two compounds for further study.

鈥淲e selected one of these compounds as a scaffold to modify into potential small molecule inhibitors of the TonB system,鈥� M. Cole Detels, an undergraduate student in Eagon鈥檚 lab, explains. The molecule is called 2-{[(3-chloro-4-methoxyphenyl)amino]methyl}quinolin-8-ol, or more simply, the 鈥渉ydroxyquinoline scaffold.鈥�

After they made the scaffold molecule, Detels and Ronquillo prepared five variations, and another three are now in the purification stage. 鈥淲hile the synthesis of the potential drugs is relatively straightforward, purifying them from the soup of other chemicals used in their preparation has been challenging,鈥� Detels says.

The team says that the goal is to prepare a library of inhibitors in which the hydroxyquinoline scaffold is modified with various functional groups. 鈥淲ith this library in hand, we will work with our collaborators to screen them against UPEC and human cell lines to look for broad toxicity,鈥� Eagon says. 鈥淎fter that, the compounds will be tested in animal models to see if they kill the bacteria in vivo.鈥� Once Eagon鈥檚 team finishes preparing the complete hydroxyquinoline library, they plan to make variations of the second scaffold molecule.

Because they target iron uptake, this new class of drugs is expected to have no effect on beneficial E. coli strains in other regions of the body. Iron is plentiful in the body in non-urinary tract locations, so hindering iron uptake shouldn鈥檛 cause a problem for these bacteria. Most current antibiotics, however, wipe out all strains, including beneficial gut flora. And because there is no TonB homolog found in humans, the possibility of toxic side effects would also be reduced compared to other antibiotics.

The researchers acknowledge support and funding from the and the .

The American Chemical 中国365bet中文官网 (ACS) is a nonprofit organization chartered by the U.S. Congress. ACS鈥� mission is to advance the broader chemistry enterprise and its practitioners for the benefit of Earth and its people. The 中国365bet中文官网 is a global leader in providing access to chemistry-related information and research through its multiple research solutions, peer-reviewed journals, scientific conferences, eBooks and weekly news periodical Chemical & Engineering News. ACS journals are among the most cited, most trusted and most read within the scientific literature; however, ACS itself does not conduct chemical research. As a specialist in scientific information solutions (including SciFinder^庐 and STN^庐), its CAS division powers global research, discovery and innovation. ACS鈥� main offices are in Washington, D.C., and Columbus, Ohio.