Abstract Title

Activity of In Silico Selected Compounds Against Escherichia coli Methylthioadenosine Nucleosidase (MTN).

Disciplines

Chemicals and Drugs | Enzymes and Coenzymes | Medicinal-Pharmaceutical Chemistry

Abstract

New antibiotics are needed to combat drug-resistant organisms, which are of particular concern in hospitals and for people who are immunocompromised. Inhibiting methylthioadenosine nucleosidase (MTN), an important bacterial enzyme in metabolism and replication, has been shown to reduce virulence and growth of several organisms, including Escherichia coli. This data suggests that drugs that target bacterial MTN may have antimicrobial applications. To find potential inhibitors of this enzyme, a diversity set of 4,000 compounds was screened against E. coli MTN using in silico methods. In this study, we have analyzed the inhibition activity of the 33 compounds from that set that had potential against MTN. Inhibition constants were determined for active inhibitors using a UV spectrophotometric assay. Compounds that were found to inhibit MTN were also screened against human MTA phosphorylase to determine their specificity and potential as selective antibiotics.

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Activity of In Silico Selected Compounds Against Escherichia coli Methylthioadenosine Nucleosidase (MTN).

New antibiotics are needed to combat drug-resistant organisms, which are of particular concern in hospitals and for people who are immunocompromised. Inhibiting methylthioadenosine nucleosidase (MTN), an important bacterial enzyme in metabolism and replication, has been shown to reduce virulence and growth of several organisms, including Escherichia coli. This data suggests that drugs that target bacterial MTN may have antimicrobial applications. To find potential inhibitors of this enzyme, a diversity set of 4,000 compounds was screened against E. coli MTN using in silico methods. In this study, we have analyzed the inhibition activity of the 33 compounds from that set that had potential against MTN. Inhibition constants were determined for active inhibitors using a UV spectrophotometric assay. Compounds that were found to inhibit MTN were also screened against human MTA phosphorylase to determine their specificity and potential as selective antibiotics.