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Dapsone in dermatology and beyond.

Wozel G, Blasum C - Arch. Dermatol. Res. (2013)

Bottom Line: Thus, dapsone clearly has dual functions of both: antimicrobial/antiprotozoal effects and anti-inflammatory features similarly to non-steroidal anti-inflammatory drugs.Moreover, attention has been paid to mechanisms by which dapsone mediates effects in more complex settings like impact of lifespan, stroke, glioblastoma, or as anticonvulsive agent.The steroid-sparing effect of dapsone is useful for numerous clinical entities.

View Article: PubMed Central - PubMed

Affiliation: Study Centre for Clinical Trials, Dermatology, Gesellschaft für Wissens- und Technologietransfer der Technischen Universität Dresden mbH, Blasewitzer Str. 43, 01307, Dresden, Germany, Gkatharina.bluemlein@uniklinikum-dresden.de.

ABSTRACT
Dapsone (4,4'-diaminodiphenylsulfone) is an aniline derivative belonging to the group of synthetic sulfones. In 1937 against the background of sulfonamide era the microbial activity of dapsone has been discovered. Shortly thereafter, the use of dapsone to treat non-pathogen-caused diseases revealed alternate antiinflammatory mechanisms that initially were elucidated by inflammatory animal models. Thus, dapsone clearly has dual functions of both: antimicrobial/antiprotozoal effects and anti-inflammatory features similarly to non-steroidal anti-inflammatory drugs. The latter capabilities primarily were used in treating chronic inflammatory disorders. Dapsone has been investigated predominantly by in vitro methods aiming to get more insights into the effect of dapsone to inflammatory effector cells, cytokines, and/or mediators, such as cellular toxic oxygen metabolism, myoloperoxidase-/halogenid system, adhesion molecules, chemotaxis, membrane-associated phospholipids, prostaglandins, leukotrienes, interleukin-8, tumor necrosis factor α, lymphocyte functions, and tumor growth. Moreover, attention has been paid to mechanisms by which dapsone mediates effects in more complex settings like impact of lifespan, stroke, glioblastoma, or as anticonvulsive agent. Additionally, there are some dermatological investigations in human being using dapsone and its metabolites (e.g., leukotriene B4-induced chemotaxis, ultraviolet-induced erythema). It could be established that dapsone metabolites by their own have anti-inflammatory properties. Pharmacology and mechanisms of action are determining factors for clinical use of dapsone chiefly in neutrophilic and/or eosinophilic dermatoses and in chronic disorders outside the field of dermatology. The steroid-sparing effect of dapsone is useful for numerous clinical entities. Future avenues of investigations will provide more information on this fascinating and essential agent.

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Chemical structure of dapsone hydroxylamine
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Fig9: Chemical structure of dapsone hydroxylamine

Mentions: Metabolism of dapsone in cell cultures has not been studied as extensively [17]. In part, this can be attributed to the chemical properties of dapsone, which make it a difficult-to-handle compound [165]. First findings concerning the metabolism of dapsone in cell cultures were presented by Drayer et al. [49] and the Canadian group of Uetrecht et al. [156]. Following incubation of PMN- and zymosan-activated human PMN with dapsone, high-pressure liquid chromatography and gas chromatography/mass spectroscopy demonstrated the production of dapsone hydroxylamine (–NO2), (Fig. 9) and a chlorine-substituted derivative of dapsone (–Cl) (chlorodapsone) (Fig. 10). Without prior stimulation, neither DDS-NOH nor the nitro derivative were detectable. The authors postulate the biotransformation as depicted in Fig. 3. Activation of leukocytes results in the induction of the respiratory burst pathway with consecutive production of reactive oxygen-species (ROS) such as 1O2 (singlet-O2), H2O2 or OH−. During this process, myeloperoxidase (MPO) uses dapsone as substrate resulting in the generation of DDS-NOH via oxidation. Finally, by a further non-enzymatic oxidation process, the nitro derivative of dapsone is generated (Fig. 11).Fig. 3


Dapsone in dermatology and beyond.

Wozel G, Blasum C - Arch. Dermatol. Res. (2013)

Chemical structure of dapsone hydroxylamine
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3927068&req=5

Fig9: Chemical structure of dapsone hydroxylamine
Mentions: Metabolism of dapsone in cell cultures has not been studied as extensively [17]. In part, this can be attributed to the chemical properties of dapsone, which make it a difficult-to-handle compound [165]. First findings concerning the metabolism of dapsone in cell cultures were presented by Drayer et al. [49] and the Canadian group of Uetrecht et al. [156]. Following incubation of PMN- and zymosan-activated human PMN with dapsone, high-pressure liquid chromatography and gas chromatography/mass spectroscopy demonstrated the production of dapsone hydroxylamine (–NO2), (Fig. 9) and a chlorine-substituted derivative of dapsone (–Cl) (chlorodapsone) (Fig. 10). Without prior stimulation, neither DDS-NOH nor the nitro derivative were detectable. The authors postulate the biotransformation as depicted in Fig. 3. Activation of leukocytes results in the induction of the respiratory burst pathway with consecutive production of reactive oxygen-species (ROS) such as 1O2 (singlet-O2), H2O2 or OH−. During this process, myeloperoxidase (MPO) uses dapsone as substrate resulting in the generation of DDS-NOH via oxidation. Finally, by a further non-enzymatic oxidation process, the nitro derivative of dapsone is generated (Fig. 11).Fig. 3

Bottom Line: Thus, dapsone clearly has dual functions of both: antimicrobial/antiprotozoal effects and anti-inflammatory features similarly to non-steroidal anti-inflammatory drugs.Moreover, attention has been paid to mechanisms by which dapsone mediates effects in more complex settings like impact of lifespan, stroke, glioblastoma, or as anticonvulsive agent.The steroid-sparing effect of dapsone is useful for numerous clinical entities.

View Article: PubMed Central - PubMed

Affiliation: Study Centre for Clinical Trials, Dermatology, Gesellschaft für Wissens- und Technologietransfer der Technischen Universität Dresden mbH, Blasewitzer Str. 43, 01307, Dresden, Germany, Gkatharina.bluemlein@uniklinikum-dresden.de.

ABSTRACT
Dapsone (4,4'-diaminodiphenylsulfone) is an aniline derivative belonging to the group of synthetic sulfones. In 1937 against the background of sulfonamide era the microbial activity of dapsone has been discovered. Shortly thereafter, the use of dapsone to treat non-pathogen-caused diseases revealed alternate antiinflammatory mechanisms that initially were elucidated by inflammatory animal models. Thus, dapsone clearly has dual functions of both: antimicrobial/antiprotozoal effects and anti-inflammatory features similarly to non-steroidal anti-inflammatory drugs. The latter capabilities primarily were used in treating chronic inflammatory disorders. Dapsone has been investigated predominantly by in vitro methods aiming to get more insights into the effect of dapsone to inflammatory effector cells, cytokines, and/or mediators, such as cellular toxic oxygen metabolism, myoloperoxidase-/halogenid system, adhesion molecules, chemotaxis, membrane-associated phospholipids, prostaglandins, leukotrienes, interleukin-8, tumor necrosis factor α, lymphocyte functions, and tumor growth. Moreover, attention has been paid to mechanisms by which dapsone mediates effects in more complex settings like impact of lifespan, stroke, glioblastoma, or as anticonvulsive agent. Additionally, there are some dermatological investigations in human being using dapsone and its metabolites (e.g., leukotriene B4-induced chemotaxis, ultraviolet-induced erythema). It could be established that dapsone metabolites by their own have anti-inflammatory properties. Pharmacology and mechanisms of action are determining factors for clinical use of dapsone chiefly in neutrophilic and/or eosinophilic dermatoses and in chronic disorders outside the field of dermatology. The steroid-sparing effect of dapsone is useful for numerous clinical entities. Future avenues of investigations will provide more information on this fascinating and essential agent.

Show MeSH
Related in: MedlinePlus