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Journal of Molecular Modeling May 2020The theoretical charge density study for the gas phase of anti-leprosy drug Dapsone has been carried out in the light of the theory of atoms in molecules using density...
The theoretical charge density study for the gas phase of anti-leprosy drug Dapsone has been carried out in the light of the theory of atoms in molecules using density functional theory employing B3LYP(6-311G++(d, p) hybrid functional completed with dispersion corrections. The Hirshfeld surface analysis as well as fingerprint plots has been utilized to visualize and quantify the intermolecular contacts present in the molecule. The topological properties such as electron density and its Laplacian, delocalization index have been elucidated to throw light into the chemical bonding and atomic and molecular details. The electron localization function has been used to visualize and deduce information on the lone pair and the subshells of the Cl atom. The electrostatic potential visualizes the positive and negative electrostatic potential regions which are susceptible to nucleophilic and electrophilic attack. On the whole, this study provides an exact mechanism, interaction, and topological and electrostatic properties of the drug through theoretical insights which all will be a platform for our further investigation of the interaction between dapsone and dihydropteroate synthase (DHPS).
Topics: Bacterial Proteins; Computational Chemistry; Dapsone; Dihydropteroate Synthase; Hydrogen Bonding; Leprostatic Agents; Models, Molecular; Molecular Docking Simulation; Mycobacterium leprae; Static Electricity
PubMed: 32415338
DOI: 10.1007/s00894-020-04393-6 -
Journal of Clinical Sleep Medicine :... Dec 2011
Topics: Ascorbic Acid; Azathioprine; Blood Gas Analysis; Dapsone; Female; Follow-Up Studies; Humans; Hypercapnia; Hypoxia; Methemoglobinemia; Methylene Blue; Middle Aged; Myositis; Oximetry; Polysomnography; Prednisone; Respiratory Function Tests; Respiratory Insufficiency; Risk Assessment; Severity of Illness Index; Treatment Outcome
PubMed: 22171210
DOI: 10.5664/jcsm.1484 -
Molecules (Basel, Switzerland) Sep 2021Dapsone (DDS) is an antibacterial drug with well-known antioxidant properties. However, the antioxidant behavior of its derivatives has not been well explored. In the...
Dapsone (DDS) is an antibacterial drug with well-known antioxidant properties. However, the antioxidant behavior of its derivatives has not been well explored. In the present work, the antioxidant activity of 10 dapsone derivatives 4-substituted was determined by an evaluation in two in vitro models (DPPH radical scavenging assay and ferric reducing antioxidant power). These imine derivatives - were obtained through condensation between DDS and the corresponding aromatic aldehydes 4-substuited. Three derivatives presented better results than DDS in the determination of DPPH (, , and ). Likewise, we have three compounds with better reducing activity than dapsone (, , and ). In order to be more insight, the redox process, a conceptual DFT analysis was carried out. Molecular descriptors such as electronic distribution, the total charge accepting/donating capacity (I/A), and the partial charge accepting/donating capacity (ω/ω) were calculated to analyze the relative donor-acceptor capacity through employing a donor acceptor map (DAM). The DFT calculation allowed us to establish a relationship between GAP and DAM with the observed antioxidant effects. According to the results, we concluded that compounds and have the lowest values, representing a good antioxidant behavior observed experimentally in DPPH radical capturing. On the other hand, derivatives , , and display the best reducing capacity activity with the highest ω and values. Consequently, we propose these compounds as the best antireductants in our DDS imine derivative series.
Topics: Antioxidants; Computer Simulation; Dapsone; Density Functional Theory; Imines; Molecular Structure; Structure-Activity Relationship
PubMed: 34641292
DOI: 10.3390/molecules26195747 -
BMJ Case Reports Feb 2021Rosai-Dorfman disease is a rare benign histiocytic proliferative disease of unknown cause that, in exceptional cases, presents with lesions confined to the skin....
Rosai-Dorfman disease is a rare benign histiocytic proliferative disease of unknown cause that, in exceptional cases, presents with lesions confined to the skin. Clinically variable types of lesions such as papules, nodules and plaques have been reported. We present a case of a 27-year-old woman with a 1-year history of erythematous papular and nodular lesions on the malar and right axillary regions, previously misdiagnosed as acne. She reported no fever, malaise or weight loss, while physical examination and laboratory workup were normal. Bacteriological and mycobacteriological cultures were negative. Histopathological findings showed dense infiltration of inflammatory cells involving the entire dermis, consisting of large macrophages with emperipolesis, S100 and CD68 positive, neutrophils, eosinophils, lymphocytes and plasma cells. The patient was treated with oral prednisolone without improvement. Dapsone was subsequently initiated with favourable clinical response. The present article aimed to emphasise the clinical and histological differential diagnosis and share the treatment experience.
Topics: Adult; Anti-Infective Agents; Dapsone; Diagnostic Errors; Emperipolesis; Eosinophils; Female; Glucocorticoids; Histiocytosis, Sinus; Humans; Prednisolone; Rare Diseases; S100 Proteins; Skin
PubMed: 33541998
DOI: 10.1136/bcr-2020-239244 -
Journal of Immunology (Baltimore, Md. :... Apr 2023Previous studies have shown that cysteine-reactive drug metabolites bind covalently with protein to activate patient T cells. However, the nature of the antigenic...
Previous studies have shown that cysteine-reactive drug metabolites bind covalently with protein to activate patient T cells. However, the nature of the antigenic determinants that interact with HLA and whether T cell stimulatory peptides contain the bound drug metabolite has not been defined. Because susceptibility to dapsone hypersensitivity is associated with the expression of HLA-B*13:01, we have designed and synthesized nitroso dapsone-modified, HLA-B*13:01 binding peptides and explored their immunogenicity using T cells from hypersensitive human patients. Cysteine-containing 9-mer peptides with high binding affinity to HLA-B*13:01 were designed (AQDCEAAAL [Pep1], AQDACEAAL [Pep2], and AQDAEACAL [Pep3]), and the cysteine residue was modified with nitroso dapsone. CD8+ T cell clones were generated and characterized in terms of phenotype, function, and cross-reactivity. Autologous APCs and C1R cells expressing HLA-B*13:01 were used to determine HLA restriction. Mass spectrometry confirmed that nitroso dapsone-peptides were modified at the appropriate site and were free of soluble dapsone and nitroso dapsone. APC HLA-B*13:01-restricted nitroso dapsone-modified Pep1- (n = 124) and Pep3-responsive (n = 48) CD8+ clones were generated. Clones proliferated and secreted effector molecules with graded concentrations of nitroso dapsone-modified Pep1 or Pep3. They also displayed reactivity against soluble nitroso dapsone, which forms adducts in situ, but not with the unmodified peptide or dapsone. Cross-reactivity was observed between nitroso dapsone-modified peptides with cysteine residues in different positions in the peptide sequence. These data characterize a drug metabolite hapten CD8+ T cell response in an HLA risk allele-restricted form of drug hypersensitivity and provide a framework for structural analysis of hapten HLA binding interactions.
Topics: Humans; Dapsone; Cysteine; CD8-Positive T-Lymphocytes; HLA-B Antigens; Drug Hypersensitivity; Peptides; Haptens
PubMed: 36881872
DOI: 10.4049/jimmunol.2200531 -
Archives of Disease in Childhood Sep 1997Pemphigus foliaceus is a skin disease in which antibodies against the cell surface of keratinocytes destroy the adhesion between epidermal cells, thereby producing...
Pemphigus foliaceus is a skin disease in which antibodies against the cell surface of keratinocytes destroy the adhesion between epidermal cells, thereby producing blisters. It is a rare disease in childhood, and treatment guidelines for juvenile pemphigus foliaceus are lacking. An 8 year old boy with pemphigus foliaceus is described. He did not respond to topical steroids, and the condition flared up when high dose oral steroids were tapered. The lesions resolved completely in four weeks on dapsone, which was maintained for nine months with no major adverse effects, except for a moderate increase of the methaemoglobin concentration at the outset of treatment. There has been no evidence of disease reactivation in more than nine months of follow up since dapsone withdrawal.
Topics: Child; Dapsone; Dermatologic Agents; Humans; Immunoglobulin G; Male; Pemphigus
PubMed: 9370909
DOI: 10.1136/adc.77.3.255 -
Chemical Research in Toxicology Mar 2023Drug-responsive T-cells are activated with the parent compound or metabolites, often via different pathways (pharmacological interaction and hapten). An obstacle to the...
Drug-responsive T-cells are activated with the parent compound or metabolites, often via different pathways (pharmacological interaction and hapten). An obstacle to the investigation of drug hypersensitivity is the scarcity of reactive metabolites for functional studies and the absence of coculture systems to generate metabolites in situ. Thus, the aim of this study was to utilize dapsone metabolite-responsive T-cells from hypersensitive patients, alongside primary human hepatocytes to drive metabolite formation, and subsequent drug-specific T-cell responses. Nitroso dapsone-responsive T-cell clones were generated from hypersensitive patients and characterized in terms of cross-reactivity and pathways of T-cell activation. Primary human hepatocytes, antigen-presenting cells, and T-cell cocultures were established in various formats with the liver and immune cells separated to avoid cell contact. Cultures were exposed to dapsone, and metabolite formation and T-cell activation were measured by LC-MS and proliferation assessment, respectively. Nitroso dapsone-responsive CD4+ T-cell clones from hypersensitive patients were found to proliferate and secrete cytokines in a dose-dependent manner when exposed to the drug metabolite. Clones were activated with nitroso dapsone-pulsed antigen-presenting cells, while fixation of antigen-presenting cells or omission of antigen-presenting cells from the assay abrogated the nitroso dapsone-specific T-cell response. Importantly, clones displayed no cross-reactivity with the parent drug. Nitroso dapsone glutathione conjugates were detected in the supernatant of hepatocyte immune cell cocultures, indicating that hepatocyte-derived metabolites are formed and transferred to the immune cell compartment. Similarly, nitroso dapsone-responsive clones were stimulated to proliferate with dapsone, when hepatocytes were added to the coculture system. Collectively, our study demonstrates the use of hepatocyte immune cell coculture systems to detect in situ metabolite formation and metabolite-specific T-cell responses. Similar systems should be used in future diagnostic and predictive assays to detect metabolite-specific T-cell responses when synthetic metabolites are not available.
Topics: Humans; Coculture Techniques; Drug Hypersensitivity; Dapsone; Liver; Hepatocytes; Lymphocyte Activation
PubMed: 36812109
DOI: 10.1021/acs.chemrestox.2c00343 -
Revue Medicale de Liege Oct 2003The subcorneal pustular dermatosis of Sneddon and Wilkinson belongs to the heterogeneous group of neutrophilic dermatosis. This unique disorder is characterized by a... (Review)
Review
The subcorneal pustular dermatosis of Sneddon and Wilkinson belongs to the heterogeneous group of neutrophilic dermatosis. This unique disorder is characterized by a superficial pustular eruption. The pustules are flaccid and aseptic. They develop predominantly on the trunk and in the groins, axillae and submammary areas. This disease is benign and chronic. However, it can be associated with some other conditions such as lymphoproliferative and myeloproliferative diseases. Dapsone is the treatment of choice to control the skin manifestations.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Chronic Disease; Dapsone; Diagnosis, Differential; Humans; Skin Diseases, Vesiculobullous
PubMed: 14677522
DOI: No ID Found -
British Journal of Clinical Pharmacology Mar 2022Human leukocyte antigens (HLA) have been linked to adverse drug reactions. Generally, HLA association is phenotype specific and is related to either liver or skin...
Human leukocyte antigens (HLA) have been linked to adverse drug reactions. Generally, HLA association is phenotype specific and is related to either liver or skin injury. HLA-A*13:01 has been linked to dapsone-induced severe cutaneous drug reactions and its role in drug-induced liver injury (DILI) is unclear. In our series, all of the four patients with immunoallergic dapsone DILI were carrying HLA-B*13:01 compared to its prevalence of 1-12% among Indians. HLA-B*13:01 plays a role not only in dapsone-induced severe cutaneous adverse reaction (SCAR) but also in dapsone-induced liver injury with immunoallergic features and highlights the role of adaptive immune response in the pathogenesis of both liver and skin injury and associated other organ involvement.
Topics: Chemical and Drug Induced Liver Injury; Chemical and Drug Induced Liver Injury, Chronic; Dapsone; HLA Antigens; HLA-B Antigens; Humans
PubMed: 34427944
DOI: 10.1111/bcp.15054 -
The Pan African Medical Journal 2022Methemoglobinemia is a common complication of dapsone poisoning. Its´ treatment usually relies on methylene blue infusion. The aim of this study was to report a case of...
Methemoglobinemia is a common complication of dapsone poisoning. Its´ treatment usually relies on methylene blue infusion. The aim of this study was to report a case of an acute dapsone poisoning with methemoglobinemia treated only with ascorbic acid and activated charcoal. A 16-year-old female voluntary ingested 3 grams of dapsone in an attempt of suicide and presented with desaturation and tachypnea. Lab findings were compatible with methemoglobinemia. After two days of treatment with ascorbic acid and activated charcoal, we observed the disappearance of desaturation and tachypnea. Methemoglobinemia can be treated with ascorbic acid and activated charcoal in limited resource settings.
Topics: Female; Humans; Adolescent; Methemoglobinemia; Dapsone; Charcoal; Ascorbic Acid; Tachypnea
PubMed: 36451721
DOI: 10.11604/pamj.2022.43.20.34069