Abstract：
: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.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Xu WC,Silverman MH,Yu XY,Wright G,Brown Ndoi
10.1016/j.bmc.2019.06.017subject
Has Abstractpub_date
2019-08-01 00:00:00pages
3209-3217issue
15eissn
0968-0896issn
1464-3391pii
S0968-0896(19)30663-7journal_volume
27pub_type
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