Pathways

Metabolites of Sulfamethoxazole are predicted with biotransformer.

Metabolites of Sulfametopyrazine are predicted with biotransformer.

Sulfanilamide is a synthetic bacteriostatic antibiotic from the sulfonamide drug class. This molecule consists of a sulfonamide functional group attached to an aniline. This drug is used to treat vulvovaginitis caused by Candida albicans even though it has a wide spectrum against most gram-positive and many gram-negative organisms. It acts by inhibiting the dihydropteroate synthase, an important enzyme in the synthesis of folic acid in bacteria. This enzyme uses para-aminobenzoic acid (PABA) to synthesize dihydropteric acid, a substrate to do folic acid. When this reaction is inhibited, the bacteria cannot produce purine anymore, resulting in the inhibition of the replication. Sulfanilamide is administered as a vaginal cream, thus it is directly absorbed through the vaginal mucosa. Side effects of this treatment include itching, burning, redness, and swelling. Long-term use of this drug may result in cancer of the thyroid gland.

Sulfaphenazole is a synthetic antibacterial from the sulfonamide drug class. This drug is indicated for the treatment of many different bacterial infections like leprosy. It is used in humans and many animals. Sulfaphenazole acts as a competitive inhibitor of dihydropteroate synthase (DHPS). This enzyme does the condensation of p-aminobenzoic acid (PABA) and dihydropteroate diphosphate. This reaction, and the ones following, results in the synthesis of folate. Folate is an important molecule for the growth of the bacteria. The inhibition of their synthesis results in the inhibition of their growth and, in the long term, their death.

Sulfasalazine is a salicylate anti-inflammatory drug used to treat Crohn's disease, severe ulcerative colitis, and rheumatoid arthritis. This drug is metabolized by intestinal bacteria to mesalazine and sulfapyridine, these two compounds carry out the main pharmacological activity of sulfasalazine. The mode of action of sulfasalazine or its metabolites, 5-aminosalicylic acid, and sulfapyridine, is still under investigation but may be related to the anti-inflammatory and/or immunomodulatory properties that have been observed in animals. Sulfasalazine and its metabolites have been shown to inhibit leukotrienes and prostaglandins by blocking the cyclo-oxygenase and lipoxygenase pathways. The enzymes that were investigated include phospholipase A2, cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX2), and arachidonate 5-lipoxygenase. The cyclooxygenase pathway begins in the cytosol with phospholipids being converted into arachidonic acid by the action of phospholipase A2. The rest of the pathway occurs on the endoplasmic reticulum membrane, where prostaglandin G/H synthase 1 & 2 convert arachidonic acid into prostaglandin H2. Prostaglandin H2 can either be converted into thromboxane A2 via thromboxane A synthase, prostacyclin/prostaglandin I2 via prostacyclin synthase, or prostaglandin E2 via prostaglandin E synthase. COX-2 is an inducible enzyme, and during inflammation, it is responsible for prostaglandin synthesis. It leads to the formation of prostaglandin E2 which is responsible for contributing to the inflammatory response by activating immune cells and for increasing pain sensation by acting on pain. Mesalazine inhibits the action of COX-1 and COX-2 on the endoplasmic reticulum membrane. This reduces the formation of prostaglandin H2 and therefore, prostaglandin E2 (PGE2). The low concentration of prostaglandin E2 attenuates the effect it has on stimulating immune cells and pain fibers, consequently reducing inflammation and pain. Fever is triggered by inflammatory and infectious diseases. Cytokines are produced in the central nervous system (CNS) during an inflammatory response. These cytokines induce COX-2 production that increases the synthesis of prostaglandin, specifically prostaglandin E2 which adjusts hypothalamic temperature control by increasing heat production. Because mesalazine decreases PGE2 in the CNS, it has an antipyretic effect. Antipyretic effects results in increased peripheral blood flow, vasodilation, and subsequent heat dissipation. Inhibitory activities on other non-arachidonic acid derivatives have also been observed, including PPAR gamma, NF-Kb, and IkappaB kinases alpha and beta.