Antibacterial nicotinamide adenine dinucleotide synthetase inhibitors: amide- and ether-linked tethered dimers with alpha-amino acid end groups

Sadanandan E Velu; Liyuan Mou; Chi-Hao Luan; Zhengrong W Yang; Lawrence J DeLucas; Christie G Brouillette; Wayne J Brouillette

doi:10.1021/jm061349l

Antibacterial nicotinamide adenine dinucleotide synthetase inhibitors: amide- and ether-linked tethered dimers with alpha-amino acid end groups

J Med Chem. 2007 May 31;50(11):2612-21. doi: 10.1021/jm061349l. Epub 2007 May 10.

Authors

Sadanandan E Velu¹, Liyuan Mou, Chi-Hao Luan, Zhengrong W Yang, Lawrence J DeLucas, Christie G Brouillette, Wayne J Brouillette

Affiliation

¹ Department of Chemistry, Center for Biophysical Sciences and Engineering, University of Alabama at Birmingham, 901 14th Street South, Birmingham, Alabama 35294, USA.

PMID: 17489580
DOI: 10.1021/jm061349l

Abstract

Tethered dimers incorporating natural alpha-amino acid end groups were synthesized, including examples in which the previously reported esterase-sensitive ester linker was replaced with more stable amide or ether linkers. These compounds remained effective both as inhibitors of NAD synthetase and as potent antibacterial agents for Gram-positive strains. Studies on nonspecific effects, including detergent properties and promiscuous inhibition, suggested little contribution to observed activities.

MeSH terms

Amide Synthases / antagonists & inhibitors*
Amide Synthases / metabolism
Amides / chemistry
Amino Acids / chemical synthesis*
Amino Acids / chemistry
Amino Acids / pharmacology
Anti-Bacterial Agents / chemical synthesis*
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology
Bacillus subtilis / enzymology
Detergents / chemistry
Dimerization
Ethers / chemistry
Gram-Positive Bacteria / drug effects*
Microbial Sensitivity Tests
NAD / metabolism*
Octoxynol / chemistry
Structure-Activity Relationship

Substances

Amides
Amino Acids
Anti-Bacterial Agents
Detergents
Ethers
NAD
Octoxynol
Amide Synthases
NAD+ synthase