The selectivity depends on the reaction conditions. The sulfone dapsone is an old antibiotic used for the treatment of mycobacterial and protozoal infections. Rapidly and almost completely absorbed from gi tract. Synthesis, characterization and antibacterial studies of. Be alert for signs of liver toxicity, including anorexia, abdominal pain, severe nausea and vomiting, yellow skin or eyes, fever, sore throat, malaise, weakness, facial edema, lethargy, and unusual bleeding or bruising.
History synthesis of dapsone was reported in 1908 by emil fromm in 1937, soon after the discovery of sulphonamides as antibiotics, two research groups one in england and one in france were the first to investigate dapsone both groups concurrently published the observed antiinflammatory potency in experimentally induced infections. We postulated before that dapsone might possess biological activity exceeding its anti. From 1936 until 1996, the drug dapsone treated a diverse array of diseases, including tuberculosis, leprosy, malaria, and aidsrelated pneumonia. It is a white, odorless crystalline powder, practically insoluble in water and insoluble in fixed and vegetable oils. Pdf dapsone 4,4diaminodiphenylsulfone is an aniline derivative belonging to the group of synthetic. Dapsone diaminodiphenyl sulfoneis a medication most commonly usedin combination with rifampicin andclofazimine as multidrug therapymdt for the treatment ofmycobacterium leprae infections leprosy. As a structural analog of paminobenzoic acid, dapsone inhibits dihydropteroate synthase dhps, an enzyme important in folate synthesis, resulting in a depletion of the folate pool and a reduction in the amount of thymidylate available for dna synthesis. Dapsone c12h12n2o2s cid 2955 structure, chemical names, physical and. Synthesis of sulfones from organozinc reagents, dabso, and. Background although dapsone was first synthesized in 1908, a quarter of a century was to pass before it was used in the treatment of bacterial infections. Dapsone fda prescribing information, side effects and uses. The antimicrobial properties of dapsone result from competitive inhibition of dihydropteroate synthase, a bacterial enzyme necessary for synthesis of folic acid.
Organozinc reagents react with the so2 surrogate dabso, and the resulting zinc sulfinate salts are alkylated in situ to afford sulfones. Dapsone should be discontinued or reduced in dosage if severe lepra reactions affecting the eyes or nerve trunks occur. Chemical synthesis 2 materials science 1 special grade. Synthesis and biological evaluation of schiff base of. Dapsone dress and genes that fit nejm journal watch. Coartem and confirmation of findings in a comparative trial of lapdap versus dacart pdf. In the literature, the effect of dapsone on the heart has only been described twice. Dapsone aczone side effects, dosage, interactions drugs. Dapsone for more information on our products custom synthesis, contact synzeal today.
A process for the synthesis of dapsone and intermediates thereof are described. Synthesis of metal complexes to a stirred solution of each ligand 0. Dapsone, also known as diaminodiphenyl sulfone dds, is an antibiotic commonly used in combination with rifampicin and clofazimine for the treatment of leprosy. This article explores how dapsone transformed from a cure for one disease into a treatment for a totally different malady. It is an antibacterial drug for susceptible cases of leprosy. This syndrome is an idiosyncratic drug reaction which occurs in 0. A short history of dapsone, or an alternative model of. Synthesis and characterization of schiff base metal.
At that time, dapsone was not envisioned as a therapeutic agent, but was the result of pure chemical. Synthesis, characterization and antibacterial activity of new series of sulfamethoxazole derivatives. A multinational team of investigators completed a genomewide association study of 872 dapsone recipients 39 with dapsoneinduced dress and 833 controls to identify risk factors associated with development of the hypersensitivity syndrome. Both single or doublet carboxamide of dapsone can be estimated in ftir, nmr and mass spectra 8. Preparation and solidstate characterization of dapsone. This mdt protocol does consider the specific type of the disease multibacillary and. As our channel brand, vwr offers an integrated, seamless purchasing experience that is. Metabolism dapsone is acetylated in the liver, the degree of which isgenetically determined.
It is normally taken once a day or three times a week. The antiinflammatory properties of dapsone result from inhibition of granulocyte cytotoxicity, via inhibition of peroxidases and scavenging of reactive oxygen species. In kinetic experiments the rate of folate synthesis was evaluated graphically from the initially linear portions of plots of the amount of folate synthesized vs. Dapsone was, however, too toxic for humans because of the excess dosage which was administered at that time and was thus considered to be of no value in the treatment of common bacterial infections. In this work, we present a novel, efficient and green methodology for the synthesis of thioethers by the cs crosscoupling reaction with the assistance of celpro 2 2 ox as a heterogeneous catalyst in good to excellent yields. Dapsone is available in tablets of 25 or 100 milligrams mg. Synthesis, characterization and antibacterial activity of. Use the link below to share a fulltext version of this article with your friends and colleagues.
Computeraided synthesis of dapsonephytochemical conjugates against dapsoneresistant mycobacterium leprae. Dapsone tablets usp, 25 mg are available as white, round tablet. Distribution approximately 70% bound to plasma protein. It is a white, odorless crystalline powder, practically insoluble in water and. General procedure for the synthesis of dapsoneprecursor specially dapsoneprecursor was carried out in gramscale, the reaction was performed using 1iodo4nitrobenzene 5 mmol and 4aminothiophenol 10 mmol in ethanol 4 ml, k2co3 25 mmol in the presence of 10% mol of cerium catalyst. The invention belongs to the field of medical chemistry, and discloses a preparation method for dapsone, wherein the method comprises the following steps. As a structural analog of paminobenzoic acid paba, dapsone inhibits dihydropteroate synthase dhps, an enzyme important in folate synthesis, resulting in a depletion of the folate pool and a reduction in the amount of thymidylate available for dna synthesis. Synthesis and antileprosy activity of some dialkyldithiocarbamates. In the early 20th century, it is invented by the german chemist paul ehrlich while working on selective toxicity. In this work, crystal engineering principles were exercised to guide the design and synthesis of the biopharmaceutics classification system class iv drug dapsone dap. Dapsone dosing, indications, interactions, adverse effects. A short history of dapsone, or an alternative model of drug development. Dapsone cas 80080, synthesis, structure, density, melting point, boiling point.
Dapsone acts as other sulfonamides, by competing with paraaminobenzoic acid for the enzyme dihydropteroate synthetase and therefore inhibiting the synthesis of dihydrofolic acid see ch. A scaleup of the protocol was explored using an unpublished methodology for the synthesis of a dapsoneprecursor, which proved to be very effective over a. Absorption it is completely absorbed after oral administration2. Pdf dapsone in dermatology and beyond researchgate. After the skin is gently washed and patted dry, apply approximately a peasized amount of. Another way of the synthesis of dapsone begins with 4acetamidobenzenesulfonic acid, which is reacted with 4chloronitrobenzene at high temperatures to give 4acetamido4. As an antibacterial, dapsone inhibits bacterial synthesis of dihydrofolic acid, via competition with paraaminobenzoate for the. The aminolysis reaction is very useful method to synthesis af amide. Find, read and cite all the research you need on researchgate. A dose of 100 mg of dapsone is weakly bactericidal against m. Docking analysis of schiff base and azetidinone of dapsone sr. A process for the synthesis of dapsone comprising the following steps. Rapid synthesis of 2cyanobenzothiazole, isothiocyanate and cyanoformanilide derivatives of dapsone. The main metabolite, monoacetyl dapsone, is nearly 100% protein bound.
Varying degrees of doserelated haemolysis and methaemoglobinaemia are the most frequently reported adverse effects of dapsone and occur in most subjects given more than 200mg daily. Dapsoneusp, 4,4diaminodiphenylsulfone dds, is a primary treatment for dermatitis herpetiformis. Pharmaceutical cocrystals involving two active pharmaceutical ingredients are rarely revealed in the literature. Dapsone dap sone is 4,4 diaminodiphenylsulfone and is bacteriostatic for mycobacterium leprae. Dapsone pharmacokinetics absorption bioavailability.
Dapsone 80080, c12h12n2o2s, density, melting point. Submitted to the department of pharmaceutical chemistry and the committee of graduate. Studies of the college of pharmacyuniversity of almustansiriyah in partial fulfillment of. Dapsone avlosulfon aids information, education, action. Dapsone is a synthetic derivative of diaminosulfone with antiinflammatory and antibacterial properties. Folate synthesis is an essential metabolic step in those unicellular organisms that, unlike humans, cannot use preformed folates. Wo2016016321a1 process for the synthesis of dapsone and. The company operates in more than 30 countries and delivers an extensive portfolio of products and services. Like other sulfonamides, dapsone is believed to act by inhibition of folate synthesis. It is a secondline medication for the treatment and prevention of pneumocystis pneumonia and for the prevention of toxoplasmosis in those who have poor immune function. Pdf sulfoximine and sulfiliminebased dapson analogues.
1235 716 91 800 628 986 42 737 343 421 656 59 26 709 927 186 1011 454 1331 1448 634 1068 1410 1352 402 410 281 1263 24 245 331 873