| Enzyme inhibitor |
This aromatic acid (FWfree-acid = 153.14 g/mol: CAS 2066-89-9; Abbreviation: PAS), also known by the trade name Paser? as well as 4- aminosalicylic acid or p-aminosalicylic acid, is an analogue of p- aminobenzoate, an essential intermediate in the bacterial folate synthesis. PAS potently inhibits the growth of Mycobacterium bovi, M. smegmatis, and M. tuberculosis. It is also used for the treatment of such inflammatory bowel diseases as ulcerative colitis and Crohn's disease, most likely by inhibiting NF-kB. Primary Mode of Antimicrobial Action: Although in use clinically for over 60 years, p-aminosalicylate’s inhibitory mechanism had proved elusive. Recent studies, however, demonstrated that PAS is prodrug, one that targets dihydrofolate reductase, or DHFR. PAS is first converted by dihydropteroate synthase (DHPS) a nd dihydrofolate synthase (DHFS) to a hydroxyl-dihydrofolate antimetabolite, which in turn inhibits DHFR. PAS is about as efficient a DHPS substrate as its natural substrate pABA, and inhibition of DHPS or mutation in DHFS prevents the formation of the antimetabolite and confers resistance to PAS. |
China
