Safety of Pyrazine-2-carboxylic acid. I found the field of Biochemistry & Molecular Biology very interesting. Saw the article Mycobacterium tuberculosis PanD Structure-Function Analysis and Identification of a Potent Pyrazinoic Acid-Derived Enzyme Inhibitor published in 2021, Reprint Addresses Gruber, G (corresponding author), Nanyang Technol Univ, Sch Biol Sci, Singapore 637551, Singapore.; Aldrich, CC (corresponding author), Univ Minnesota, Coll Pharm, Dept Med Chem, Minneapolis, MN 55455 USA.; Dick, T (corresponding author), Hackensack Meridian Hlth, Ctr Discovery & Innovat, Nutley, NJ 07110 USA.; Dick, T (corresponding author), Hackensack Meridian Sch Med, Dept Med Sci, Nutley, NJ 07110 USA.; Dick, T (corresponding author), Georgetown Univ, Dept Microbiol & Immunol, Washington, DC 20007 USA.. The CAS is 98-97-5. Through research, I have a further understanding and discovery of Pyrazine-2-carboxylic acid.
A common strategy employed in antibacterial drug discovery is the targeting of biosynthetic processes that are essential and specific for the pathogen. Specificity in particular avoids undesirable interactions with potential enzymatic counterparts in the human host, and it ensures ontarget toxicity. Synthesis of pantothenate (Vitamine B5), which is a precursor of the acyl carrier coenzyme A, is an example of such a pathway. In Mycobacterium tuberculosis (Mtb), which is the causative agent of tuberculosis (TB), pantothenate is formed by pantothenate synthase, utilizing D-pantoate and beta-Ala as substrates. beta-Ala is mainly formed by the decarboxylation of L-aspartate, generated by the decarboxylase PanD, which is a homo-oliogomer in solution. Pyrazinoic acid (POA), which is the bioactive form of the TB prodrug pyrazinamide, binds and inhibits PanD activity weakly. Here, we generated a library of recombinant Mtb PanD mutants based on structural information and PZA/POA resistance mutants. Alterations in oligomer formation, enzyme activity, and/or POA binding were observed in respective mutants, providing insights into essential amino acids for Mtb PanD’s proper structural assembly, decarboxylation activity and drug interaction. This information provided the platform for the design of novel POA analogues with modifications at position 3 of the pyrazine ring. Analogue 2, which incorporates a bulky naphthamido group at this position, displayed a 1000-fold increase in enzyme inhibition, compared to POA, along with moderately improved antimycobacterial activity. The data demonstrate that an improved understanding of mechanistic and enzymatic features of key metabolic enzymes can stimulate design of more-potent PanD inhibitors.
Welcome to talk about 98-97-5, If you have any questions, you can contact Ragunathan, P; Cole, M; Latka, C; Aragaw, WW; Hegde, P; Shin, J; Manimekalai, MSS; Rishikesan, S; Aldrich, CC; Dick, T; Gruber, G or send Email.. Safety of Pyrazine-2-carboxylic acid
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Patent; Chevron Research Company; US4732894; (1988); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem