Leishmanicidal and Immunomodulatory Activities of the Palladacycle Complex DPPE 1.1, a Potential Candidate for Treatment of Cutaneous Leishmaniasis

Santos, Isabela B Dos; Silva, Danielle A M da; Paz, Fabiana A C R; Garcia, Daniel M.; Carmona, Adriana K.; Teixeira, Daniela; Longo-Maugéri, Ieda Maria; Katz, Simone; Barbiéri, Clara Lúcia

doi:10.3389/fmicb.2018.01427

Cited by 9 publications

(5 citation statements)

References 51 publications

(59 reference statements)

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“…It is reported that aziridine-2,3-dicarboxylate [180], natural products flavone derivatives [181], trans-aziridine-2,3-dicarboxylate derivatives [182] organotellurane RF07 and palladacycle complex [183][184][185], and dipeptidyl enoates [186] exhibit antileishmanial effect and inhibit cysteine proteases.…”

Section: Cysteine Proteasesmentioning

confidence: 99%

Toward New Antileishmanial Compounds: Molecular Targets for Leishmaniasis Treatment

Istanbullu¹,

Bayraktar²

2022

Leishmaniasis - General Aspects of a Stigmatized Disease

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The leishmaniases are a group of diseases caused by protozoan parasites—Leishmania sp. Leishmaniasis is classified among the 20 neglected diseases by WHO. Although the disease has been known for more than 120 years, the number of drugs used for the treatment is still limited to 5–6. The first-line drugs against leishmaniasis are pentavalent antimonials, which were introduced to the treatment 70 years ago—despite all their side effects. Molecular targets are becoming increasingly important for efficacy and selectivity in postgenomic drug research studies. In this chapter, we have discussed potential therapeutic targets of antileishmanial drug discovery such as pteridine reductase (PTR1), trypanothione reductase (TR), N-myristoyltransferase (NMT), trypanothione synthetase (TryS), IU-nucleoside hydrolase, and topoisomerases, enzymes and their inhibitors reported in the literature.

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Section: Cysteine Proteasesmentioning

confidence: 99%

Toward New Antileishmanial Compounds: Molecular Targets for Leishmaniasis Treatment

Istanbullu¹,

Bayraktar²

2022

Leishmaniasis - General Aspects of a Stigmatized Disease

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“…Hence, host directed therapies, which directly modulate the immune response against parasites could be novel treatments for different forms of CL. Efficacy of immunomodulators in the treatment of CL has not only been demonstrated in experimental animal studies ( Buates and Matlashewski, 1999 ), but also in patients ( Chouhan et al., 2014 ; Dos Santos et al., 2018 ; Caridha et al., 2019 ; Nahidi et al., 2021 ). Immunotherapy can also be a suitable option for patients with clinical resistance to recommended drugs; for example, patients from Peru with resistance to antimony showed a faster resolution of CL lesions after the use of the TLR7 agonist imiquimod ( Miranda-Verástegui et al., 2005 ).…”

Section: Conclusion and Final Remarksmentioning

confidence: 99%

Mechanisms of Immunopathogenesis in Cutaneous Leishmaniasis And Post Kala-azar Dermal Leishmaniasis (PKDL)

Volpedo

Pacheco-Fernández

Holcomb

et al. 2021

Front. Cell. Infect. Microbiol.

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Leishmaniasis is a neglected tropical disease that affects 12 million people worldwide. The disease has high morbidity and mortality rates and is prevalent in over 80 countries, leaving more than 300 million people at risk of infection. Of all of the manifestations of this disease, cutaneous leishmaniasis (CL) is the most common form and it presents as ulcerating skin lesions that can self-heal or become chronic, leading to disfiguring scars. This review focuses on the different pathologies and disease manifestations of CL, as well as their varying degrees of severity. In particular, this review will discuss self-healing localized cutaneous leishmaniasis (LCL), leishmaniasis recidivans (LR), mucocutaneous leishmaniasis (MCL), anergic diffuse cutaneous leishmaniasis (ADCL), disseminated leishmaniasis (DL), and Post Kala-azar Dermal Leishmaniasis (PKDL), which is a cutaneous manifestation observed in some visceral leishmaniasis (VL) patients after successful treatment. The different clinical manifestations of CL are determined by a variety of factors including the species of the parasites and the host’s immune response. Specifically, the balance between the pro and anti-inflammatory mediators plays a vital role in the clinical presentation and outcome of the disease. Depending upon the immune response, Leishmania infection can also transition from one form of the disease to another. In this review, different forms of cutaneous Leishmania infections and their immunology are described.

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Section: Introductionmentioning

confidence: 95%

“…The activity of two palladacycle complexes, DPPE 1.1 and DPPE 1.2, was previously demonstrated on in vitro and in vivo L. (L.) amazonensis infection (14,15). The leishmanicidal effect of these palladacycle complexes is followed by activation of immune responses mediated by an increase of CD4 + and CD8 + T lymphocytes in treated animals (15,16). A significant increase in the leishmanicidal effect of DPPE 1.2 as well as of inflammatory responses was observed when this palladacycle complex was associated with heat-killed-P. acnes suspension for treatment of L. (L.) amazonensisinfected BALB/c and C57BL/6 mice (16).…”

Section: Introductionmentioning

confidence: 97%

Protective Cellular Immune Response Induction for Cutaneous Leishmaniasis by a New Immunochemotherapy Schedule

et al. 2020

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The palladacycle complex DPPE 1.2 was previously shown to inhibit Leishmania (Leishmania) amazonensis infection in vitro and in vivo. The present study aimed to evaluate the effect of DPPE 1.2 associated with a recombinant cysteine proteinase, rLdccys1, and the adjuvant Propionibacterium acnes on L. (L.) amazonensis infection in two mouse strains, BALB/c, and C57BL/6. Treatment with this association potentiated the leishmanicidal effect of DPPE 1.2 resulting in a reduction of parasite load in both strains of mice which was higher compared to that found in groups treated with either DPPE 1.2 alone or associated with P. acnes or rLdccys1. The reduction of parasite load in both mice strains was followed by immunomodulation mediated by an increase of memory CD4 + and CD8 + T lymphocytes, IFN-γ levels and reduction of active TGF-β in treated animals. No infection relapse was observed 1 month after the end of treatment in mice which received DPPE 1.2 associated with rLdccys1 or rLdccys1 plus P. acnes in comparison to that exhibited by animals treated with DPPE 1.2 alone. Evaluation of serum levels of AST, ALT, urea, and creatinine showed no alterations among treated groups, indicating that this treatment schedule did not induce hepato or nephrotoxicity. These data indicate the potential use of this association as a therapeutic alternative for cutaneous leishmaniasis caused by L. (L) amazonensis.

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Leishmanicidal and Immunomodulatory Activities of the Palladacycle Complex DPPE 1.1, a Potential Candidate for Treatment of Cutaneous Leishmaniasis

Cited by 9 publications

References 51 publications

Toward New Antileishmanial Compounds: Molecular Targets for Leishmaniasis Treatment

Toward New Antileishmanial Compounds: Molecular Targets for Leishmaniasis Treatment

Mechanisms of Immunopathogenesis in Cutaneous Leishmaniasis And Post Kala-azar Dermal Leishmaniasis (PKDL)

Protective Cellular Immune Response Induction for Cutaneous Leishmaniasis by a New Immunochemotherapy Schedule

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