Xanthine-Guanine-Hypoxanthine Phosphoribosyltransferase-A Putative Target for Drug Discovery against Gastrointestinal Tract Infections.

(Hp) is a human pathogen that lives in the gastric mucosa of approximately 50% of the world's population causing gastritis, peptic ulcers, and gastric cancer. An increase in resistance to current drugs has sparked the search for new Hp drug targets and therapeutics. One target is the disruption of nucleic acid production, which can be achieved by impeding the synthesis of 6-oxopurine nucleoside monophosphates, the precursors of DNA and RNA.

Analogues of the Herbicide, -Hydroxy--isopropyloxamate, Inhibit Ketol-Acid Reductoisomerase and Their Prodrugs Are Promising Anti-TB Drug Leads.

New drugs to treat tuberculosis (TB) are urgently needed to combat the increase in resistance observed among the current first-line and second-line treatments. Here, we propose ketol-acid reductoisomerase (KARI) as a target for anti-TB drug discovery. Twenty-two analogues of IpOHA, an inhibitor of plant KARI, were evaluated as antimycobacterial agents.

Discovery of a Pyrimidinedione Derivative with Potent Inhibitory Activity against Mycobacterium tuberculosis Ketol-Acid Reductoisomerase.

New drugs aimed at novel targets are urgently needed to combat the increasing rate of drug-resistant tuberculosis (TB). Herein, the National Cancer Institute Developmental Therapeutic Program (NCI-DTP) chemical library was screened against a promising new target, ketol-acid reductoisomerase (KARI), the second enzyme in the branched-chain amino acid (BCAA) biosynthesis pathway. From this library, 6-hydroxy-2-methylthiazolo[4,5-d]pyrimidine-5,7(4H,6H)-dione (NSC116565) was identified as a potent time-dependent inhibitor of Mycobacterium tuberculosis (Mt) KARI with a K of 95.

Herbicides That Target Acetohydroxyacid Synthase Are Potent Inhibitors of the Growth of Drug-Resistant .

Acetohydroxyacid synthase (AHAS, EC 2.2.1.

Inhibition studies of ketol-acid reductoisomerases from pathogenic microorganisms.

Ketol-acid reductoisomerase (KARI), the second enzyme in the branched-chain amino acid (BCAA) biosynthesis pathway, is an emerging target for the discovery of biocides. Here, we demonstrate that cyclopropane-1,1-dicarboxylate (CPD) inhibits KARIs from the pathogens Mycobacterium tuberculosis (Mt) and Campylobacter jejuni (Cj) reversibly with K values of 3.03 μM and 0.

Crystal structure of Mycobacterium tuberculosis ketol-acid reductoisomerase at 1.0 Å resolution - a potential target for anti-tuberculosis drug discovery.

Unlabelled: The biosynthetic pathway for the branched-chain amino acids is present in plants, fungi and bacteria, but not in animals, making it an attractive target for herbicidal and antimicrobial drug discovery. Ketol-acid reductoisomerase (KARI; EC 1.1.