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SAR studies for a new class of antibacterial NAD biosynthesis inhibitors.

ABSTRACT: A new lead class of antibacterial drug-like NAD synthetase (NADs) inhibitors was previously identified from a virtual screening study. Here a solution-phase synthetic library of 76 compounds, analogs of the urea-sulfonamide 5838, was synthesized in parallel to explore SAR on the sulfonamide aryl group. All library members were tested for enzyme inhibition against NADs and nicotinic acid mononucleotide adenylyltransferase (NaMNAT), the last two enzymes in the biosynthesis of NAD, and for growth inhibition in a Bacillus anthracis antibacterial assay. Most compounds that inhibited bacterial growth also showed inhibition against one of the enzymes tested. While only modest enhancements in the enzyme inhibition potency against NADs were observed, of significance was the observation that the antibacterial urea-sulfonamides more consistently inhibited NaMNAT.

SUBMITTER: Moro WB

PROVIDER: S-EPMC2888690 | biostudies-literature | 2009 Jul-Aug

REPOSITORIES: biostudies-literature

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SAR studies for a new class of antibacterial NAD biosynthesis inhibitors.

Moro Whitney Beysselance WB Yang Zhengrong Z Kane Tasha A TA Zhou Qingxian Q Harville Steve S Brouillette Christie G CG Brouillette Wayne J WJ

Journal of combinatorial chemistry 20090701 4

A new lead class of antibacterial drug-like NAD synthetase (NADs) inhibitors was previously identified from a virtual screening study. Here a solution-phase synthetic library of 76 compounds, analogs of the urea-sulfonamide 5838, was synthesized in parallel to explore SAR on the sulfonamide aryl group. All library members were tested for enzyme inhibition against NADs and nicotinic acid mononucleotide adenylyltransferase (NaMNAT), the last two enzymes in the biosynthesis of NAD, and for growth i ...[more]

PMID: 19408950

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SAR studies for a new class of antibacterial NAD biosynthesis inhibitors.

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SAR studies for a new class of antibacterial NAD biosynthesis inhibitors.

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