Binding of Dapsone and its Analogues to Human Serum Albumin

Karp, Warren B.; Subramanyam, S.B.; Robertson, Alex

doi:10.1002/jps.2600740624

Cited by 9 publications

(7 citation statements)

References 4 publications

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“…We also observed leucocytosis (69%), low hemoglobin (46%), and high reticulocyte count (15%). Approximately half of our patients had hypoalbuminemia, which is a feature of DHS and is probably due to the binding of dapsone to the circulating serum albumin (23).…”

Section: Discussionmentioning

confidence: 99%

Dapsone Hypersensitivity Syndrome: A Clinico-Epidemiological Review

Agrawal

Agarwalla

2005

The Journal of Dermatology

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Diaminodiphenyl sulphone (dapsone) is a drug of choice in the treatment of leprosy. It is also useful for the treatment of many neutrophilic and other dermatoses. Dapsone hypersensitivity syndrome is a rare but well recognized serious adverse effect characterized by fever, skin rashes, generalized lymphadenopathy, hepatitis, and hepato-splenomegaly. Twenty-six patients with dapsone hypersensitivity syndrome were studied for clinical profile, outcome, and prognosis. The male:female ratio was 2.2:1, and the mean age was 33.19 years (range 13 to 64 years). The interval between start of dapsone therapy and appearance of symptoms varied from 2-7 weeks (mean 29.82 days). Twenty-four patients received dapsone as a part of multi-drug therapy for leprosy; the other two patients received dapsone for lichen planus and acne vulgaris. Exfoliative dermatitis was the most common cutaneous manifestation followed by erythematous maculo-papular eruption and Stevens-Johnson syndrome-like lesion. The other common systemic manifestations were: fever (26 cases), itching (22 cases), lymphadenopathy (21 cases), jaundice (21 cases), pallor (20 cases), hepatomegaly (19 cases), and pedal edema (14 cases). Investigation profile revealed elevated levels of serum liver enzymes in 100% of patients, elevated erythrocyte sedimentation rate in 92.3%, raised bilirubin in 84.6%, leucocytosis in 69.23%, low hemoglobin (<9 gm/dl) in 46.15% and hypoproteinemia in 42.3%. Eosinophilia, hemolytic anemia, and reticulocytosis count were found in 4 patients each. All the patients had favorable outcomes except three who died due to hepatic failure. Medical personnel must be aware of this potentially fatal syndrome, because it can cause considerable morbidity and mortality.

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Section: Discussionmentioning

confidence: 99%

Dapsone Hypersensitivity Syndrome: A Clinico-Epidemiological Review

Agrawal

Agarwalla

2005

The Journal of Dermatology

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“…A plethora of studies have been conducted to investigate the interaction of various antitumor, anticancer, antiviral, and anti‐inflammatory drugs with DNA as well as serum albumin (bovine or human) protein [30–41]. Moreover, the interaction between three antimycobacterial drugs (dapsone, clofazimine, and rifampicin) and bovine or human serum albumin (HSA or BSA) have also been evidenced by different groups of scientists [42–47]. All these studies revealed that the stoichiometry of these three antimycobacterial drugs binding to HSA/BSA is approximately 1 : 1 in nature [42–47].…”

Section: Resultsmentioning

confidence: 99%

Interaction of constituents of MDT regimen for leprosy with Mycobacterium leprae HSP18: impact on its structure and function

2021

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Mycobacterium leprae, the causative organism of leprosy, harbors many antigenic proteins, and one such protein is the 18-kDa antigen. This protein belongs to the small heat shock protein family and is commonly known as HSP18. Its chaperone function plays an important role in the growth and survival of M. leprae inside infected hosts. HSP18/18-kDa antigen is often used as a diagnostic marker for determining the efficacy of multidrug therapy (MDT) in leprosy. However, whether MDT drugs (dapsone, clofazimine, and rifampicin) do interact with HSP18 and how these interactions affect its structure and chaperone function is still unclear. Here, we report evidence of HSP18-dapsone/clofazimine/rifampicin interaction and its impact on the structure and chaperone function of HSP18. These three drugs interact efficiently with HSP18 (having submicromolar binding affinity) with 1 : 1 stoichiometry. Binding of these MDT drugs to the 'α-crystallin domain' of HSP18 alters its secondary structure and tryptophan micro-environment. Furthermore, surface hydrophobicity, oligomeric size, and thermostability of the protein are reduced upon interaction with these three drugs. Eventually, all these structural alterations synergistically decrease the chaperone function of HSP18. Interestingly, the effect of rifampicin on the structure, stability, and chaperone function of this mycobacterial small heat shock protein is more pronounced than the other two MDT drugs. This reduction in the chaperone function of HSP18 may additionally abate M. leprae survivability during multidrug treatment. Altogether, this study provides a possible foundation for rational designing and development of suitable HSP18 inhibitors in the context of effective treatment of leprosy.

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“…Dicoumarol, iopanoic acid and rifampicin [39] were able to decrease the binding constant of warfarin to albumin. Ceftriaxone [40], bumetanide [41] and dapsone [42] decreased the binding of bilirubin to albumin. So these molecules are considered as ligands of site I.…”

Section: Discussionmentioning

confidence: 99%

Reviewing the binding of a series of parabens to human serum albumin

Greige‐Gerges

Kaissi

Magdalou

et al. 2013

Biopharm & Drug Disp

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To better understand the factors that contribute to the accumulation of unmetabolized parabens (p-hydroxybenzoic acid esters) in breast cancer tissue, the binding of a series of parabens (methyl-, ethyl-, butyl-, benzyl-paraben) to human serum albumin (HSA) was investigated by fluorescence spectroscopy and also their ability to modify the binding parameters of albumin site markers. Emission spectra of HSA upon fluorescence excitation of Trp 214 residue at 295 nm were recorded at different molar ratios of PB/HSA and data were corrected for the inner-filter effect. A significant inner-filter effect was obtained for molar ratios of 2.0 and above. For lower molar ratios, a slight increase in fluorescence of HSA was detected. p-Hydroxybenzoic acid, the main metabolite of parabens, did not modify the fluorescence of HSA whatever the molar ratio used. Binding parameters for compounds that are markers of site I, bilirubin and warfarin, were determined in the absence and presence of methyl, butyl and benzyl paraben at molar ratios of PB/HSA of 0, 1 and 2. No variation of the binding constants of these markers was observed. The results indicate that parabens weakly interact with HSA thus suggesting that they are in a free form in blood and therefore more available to reach tissues.

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Binding of Dapsone and its Analogues to Human Serum Albumin

Cited by 9 publications

References 4 publications

Dapsone Hypersensitivity Syndrome: A Clinico-Epidemiological Review

Dapsone Hypersensitivity Syndrome: A Clinico-Epidemiological Review

Interaction of constituents of MDT regimen for leprosy with Mycobacterium leprae HSP18: impact on its structure and function

Reviewing the binding of a series of parabens to human serum albumin

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