Originator
Sulfaguanidine,Lederle,US,1941
Definition
ChEBI: Sulfaguanidine is a sulfonamide incorporating a guanidine moiety used to block the synthesis of folic acid; mostly used in veterinary medicine It has a role as an antiinfective agent.
Manufacturing Process
10 parts of guanidine hydrochloride (0.1 mol) was dissolved in 75 parts of
water and the pH adjusted to 8 to 9. The solution was warmed to 50°C to
60°C and kept at this temperature while a slurry of 25 parts (0.113 mol) of pnitrobenzenesulfonyl
chloride was added slowly with mechanical stirring. The
pH was kept at 8 to 9 by the addition of 40% sodium hydroxide solution. At
the end of the reaction the solution was cooled and filtered from the
separated solid. The p-nitrobenzene sulfonyl guanidine was recrystallized from
hot water.
5 parts (0.024 mol) of p-nitrobenzene sulfonyl guanidine was dissolved in 50
parts of boiling 95% alcohol and to the solution was added 0.5 part of
concentrated hydrochloric acid. The solution was heated to reflux and 6 parts
of iron dust was added. The suspension was refluxed for 3 hours, made basic
with potassium carbonate, and filtered hot. The alcohol was evaporated off
and the p-aminobenzene sulfonyl guanidine recrystallized from boiling water
with the addition of decolorizing charcoal.
Brand name
Aseptil-guanidina;Coliseptale;Devaguanil;Dirkan;Emerin;Ente-rivo simplex;Granidan;Guamide;Guanicil;Guanimycin;Guanowept;Guasept;Inorgan;Intestovet;Ordenol;Orgaguanidon;Resulfon;Ruocil;Sgd;S-guanidan;S-guanidine;Shigatox;Suganyl;Sulfacarbon;Sulfentidine;Sulfogua;Tetrawest;Trisulvet.
Therapeutic Function
Antimicrobial
World Health Organization (WHO)
Sulfaguanidine, a sulfonamide anti-infective agent, was
introduced in 1941 for the treatment of bacterial infections. The importance of
sulfonamides has subsequently decreased as a result of increasing bacterial
resistance and their replacement by antibiotics which are generally more active
and less toxic. The sulfonamides are known to cause serious adverse effects such
as renal toxicity sometimes fatal exfoliative dermatitis and erythema multiforma
and dangerous adverse reactions affecting blood formation such as
agranulocytosis and haemolytic or aplastic anaemia. Although sulfaguanidine,
which is poorly absorbed from the gastrointestinal tract, is no longer
recommended in some countries, it continues to be used in others for the
treatment of local intestinal infections, including bacterial dysentery, and for preoperative bowel preparation.
Pharmaceutical Applications
1-Sulfanilylguanidine. A poorly absorbed compound, less
potent than succinylsulfathiazole but with similar uses. Blood
concentrations of 15–40 mg/L have been found after single
doses of 1–7 g. Excretion in the urine is rapid.
Biological Activity
Sulfaguanidine is a sulfonamide antibiotic. Sulfonamides block the synthesis of dihydrofolic acid by inhibiting the enzyme dihydropteroate synthase. Sulfonamides are competitive inhibitors of bacterial para-aminobenzoic acid (PABA)which is required for bacterial synthesis of folic acid. Sulfaguanidine is a dihydrofolate reductase (DHFR) inhibitor. Sulfonamides are active against Gram positive bacteria and Gram negative bacteria. Mode of resistance is via the alteration of dihydropteroate synthase or alternative pathway for folic acid synthesis.
Purification Methods
Crystallise the antibacterial from hot water (7mL/g). [Beilstein 14 III 1970, 14 IV 2668.]
