Pharmaceutical Science


Publications (4)

Evaluation of Bronopol and Disulfiram as Potential Candidatus Liberibacter asiaticus Inosine 5′-Monophosphate Dehydrogenase Inhibitors by Using Molecular Docking and Enzyme Kinetic

Citation
Nan et al. (2020). Molecules 25 (10)
Names
Ca. Liberibacter asiaticus
Subjects
Analytical Chemistry Chemistry (miscellaneous) Drug Discovery Molecular Medicine Organic Chemistry Pharmaceutical Science Physical and Theoretical Chemistry
Abstract
Citrus huanglongbing (HLB) is a destructive disease that causes significant damage to many citrus producing areas worldwide. To date, no strategy against this disease has been established. Inosine 5′-monophosphate dehydrogenase (IMPDH) plays crucial roles in the de novo synthesis of guanine nucleotides. This enzyme is used as a potential target to treat bacterial infection. In this study, the crystal structure of a deletion mutant of CLas IMPDHΔ98-201 in the apo form was determined. Eight known bioactive compounds were used as ligands for molecular docking. The results showed that bronopol and disulfiram bound to CLas IMPDHΔ98-201 with high affinity. These compounds were tested for their inhibition against CLas IMPDHΔ98-201 activity. Bronopol and disulfiram showed high inhibition at nanomolar concentrations, and bronopol was found to be the most potent molecule (Ki = 234 nM). The Ki value of disulfiram was 616 nM. These results suggest that bronopol and disulfiram can be considered potential candidate agents for the development of CLas inhibitors.