Development of Novel Bacterial Topoisomerase Inhibitors Assisted by Computational Screening
Year: 2024
Type: article
Abstract: Multidrug-resistant bacterial infections pose an ever-evolving threat to public health. Since the outset of the antibacterial age, bacteria have developed a multitude of diverse resistance mechanisms that suppress the effectiveness of current therapies. New drug entities, such as Novel Bacterial Topoisomerase Inhibitors (NBTIs), can circumvent this major issue. A computational docking model was employed to predict the binding to DNA gyrase of atypical NBTIs with novel pharmacophores. Synthesis of NBTIs based on computational docking and subsequent antibacterial evaluation against both Gram-positive and Gram-negative bacteria yielded congeners with outstanding anti-staphylococcal activity and varying activity against select Gram-negative pathogens.
Source: ACS Medicinal Chemistry Letters
Institutions: The Ohio State University, Vanderbilt University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Awards: Novel Bacterial Topoisomerase Inhibitors Targeting Gram-Negative Bacteria, Overcoming Resistance to Novel Bacterial Topoisomerase Inhibitors, Mechanistic Studies of Type II Topoisomerases and Topoisomerase-Targeted Agents, Mechanistic Studies of Gyrase/Topoisomerase IV-Targeted Antibacterials
OpenAlex ID: W4400640259