GyrB ATPase activity

AZD5099 is an orally effective pyrrole amide inhibitor and antibacterial agent. AZD5099 shows over 10000-fold higher selectivity for bacterial type II topoisomerases than for human topoisomerase IIα, with a IC₅₀ value of 0.032 μmol/L against Staphylococcus aureus GyrB, a IC₅₀ of 0.760 μmol/L against Escherichia coli GyrB, a IC₅₀ of 73 nM against Escherichia coli ParE, a K_d of 83.8 nmol/L for Staphylococcus aureus GyrB, and a IC₅₀ of >50 μM against human topoisomerase IIα. AZD5099 inhibits rat Mrp2 ATPase activity, competitively binds to the ATP-binding site of bacterial type II topoisomerases, blocks enzyme activity, reduces bacterial DNA and RNA synthesis, disrupts DNA replication and transcription processes, and induces mitochondrial toxicity. AZD5099 exhibits activity against Gram-positive bacteria, fastidious Gram-negative bacteria and drug-resistant strains, reduces bacterial loads in mouse infection models, and has a low spontaneous resistance frequency. AZD5099 can be used in studies related to infections caused by Gram-positive bacteria and fastidious Gram-negative bacteria, methicillin-resistant Staphylococcus aureus infections, Streptococcus pneumoniae pulmonary infections, as well as Staphylococcus aureus and Escherichia coli infections .

GyrB-IN-1 is a DNA gyrase (GyrB) inhibitor. GyrB-IN-1 shows an IC₅₀ of 19.1 μM against Mycobacterium smegmatis GyrB ATPase activity and 21.9 μM against Mycobacterium tuberculosis GyrB DNA supercoiling activity. GyrB-IN-1 exerts antimycobacterial activity and has cytotoxicity. GyrB-IN-1 can be used for the research of tuberculosis .

Antibacterial agent 338 (Compound 65) is an antibacterial agent and GyrB inhibitor, with an IC₅₀ of 12.60 nM against GyrB from E. coli. Antibacterial agent 338 binds to the ATP-binding domain of E. coli GyrB, thereby inhibiting the ATPase activity of GyrB. Antibacterial agent 338 exhibits broad-spectrum antibacterial activity against multidrug-resistant Gram-negative bacteria. Antibacterial agent 338 reduces bacterial load in a neutropenic mouse thigh infection model. Antibacterial agent 338 can be used for the research of Acinetobacter baumannii infection .