Discovery and development of DNA polymerase IIIC inhibitors to treat Gram-positive infections
| Autor: | Xiang Yang Yu, Michael H. Silverman, Wei-Chu Xu, George E. Wright, Neal C. Brown |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
medicine.drug_class
DNA polymerase Clinical Biochemistry Antibiotics Pharmaceutical Science Microbial Sensitivity Tests medicine.disease_cause 01 natural sciences Biochemistry chemistry.chemical_compound Antibiotic resistance Drug Discovery medicine Humans Uracil Molecular Biology Polymerase DNA Polymerase III Nucleic Acid Synthesis Inhibitors biology 010405 organic chemistry Drug candidate Clostridioides difficile Organic Chemistry Pathogenic bacteria Virology 0104 chemical sciences 010404 medicinal & biomolecular chemistry Mechanism of action chemistry biology.protein Clostridium Infections Molecular Medicine medicine.symptom |
| Zdroj: | Bioorganicmedicinal chemistry. 27(15) |
| ISSN: | 1464-3391 |
| Popis: | Despite the growing global crisis caused by antimicrobial drug resistance among pathogenic bacteria, the number of new antibiotics, especially new chemical class of antibiotics under development is insufficient to tackle the problem. Our review focuses on an emerging class of antibacterial therapeutic agents that holds a completely novel mechanism of action, namely, inhibition of bacterial DNA polymerase IIIC. The recent entry of this new class into human trials may herald the introduction of novel drugs whose novel molecular target precludes cross-resistance with existing antibiotic classes. This review therefore examines the evolution of DNA pol IIIC inhibitors from the discovery of 6-(p-hydroxyphenylazo)uracil (HPUra) in the 1960s to the development of current first-in-class N7-substituted guanine drug candidate ACX-362E, now under clinical development for the treatment of Clostridioides difficile infection. |
| Databáze: | OpenAIRE |
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