Developments in Diagnosis and Antileishmanial Drugs

Bhargava, Prachi; Singh, Rajni

doi:10.1155/2012/626838

Cited by 50 publications

(24 citation statements)

References 107 publications

(93 reference statements)

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“…Leishmaniasis, a neglected tropical disease that affects 2 million people every year, 118 has attracted special attention in the recent years due to the outbreak of Leishmania spp. resistant to current antimony-based therapy.…”

Section: Aminoglycosides As Antiprotozoal Agents: the Fight Against Lmentioning

confidence: 99%

New trends in the use of aminoglycosides

Fosso

2014

Med. Chem. Commun.

100

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Despite their inherent toxicity and the acquired bacterial resistance that continuously threaten their long-term clinical use, aminoglycosides (AGs) still remain valuable components of the antibiotic armamentarium. Recent literature shows that the AGs’ role has been further expanded as multi-tasking players in different areas of study. This review aims at presenting some of the new trends observed in the use of AGs in the past decade, along with the current understanding of their mechanisms of action in various bacterial and eukaryotic cellular processes.

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Section: Aminoglycosides As Antiprotozoal Agents: the Fight Against Lmentioning

confidence: 99%

New trends in the use of aminoglycosides

Fosso

2014

Med. Chem. Commun.

100

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“…Leishmaniasis a group of diseases caused by trypanosomatids from the genus Leishmania . The disease is found endemic in 88 countries all over the world, affecting 12 million people with an estimated 1·5–2·0 million new cases and 80 000 deaths each year . The disease is epidemiologically very diverse due to the large number of parasite species of genus Leishmania which are pathogenic to humans .…”

Section: Introductionmentioning

confidence: 99%

To investigate the therapeutic potential of immunochemotherapy with cisplatin + 78 kDa + MPL‐A against Leishmania donovani in BALB/c mice

Joshi

Kaur

2013

Parasite Immunology

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Leishmaniasis has recently garnered attention as one of the diseases 'most neglected' by drug research and development, as the current therapeutic modalities available for the patients are ridden with unacceptable toxicity due to high dosage of the drug, prolonged treatment schedules, resistance and prohibitive costs. A successful chemotherapy requires a restoration of immune response; therefore, we combined Leishmania-specific 78 kDa antigen (with or without adjuvant MPL-A) along with a novel drug cisplatin in infected BALB/c mice and did its comparative analysis with chemotherapy and immunotherapy alone. Animals that were treated with immunochemotherapy showed maximum curative potential as demonstrated by a marked reduction in parasite load. Delayed-type hypersensitivity response to leishmanial antigens has been widely used to assess the level of host protection to the disease. An increased delayed-type hypersensitivity (DTH) response was observed in animals given immunotherapy or chemotherapy or immunochemotherapy; however, maximum DTH response was observed in animals treated with cisplatin + 78 kDa + MPL-A. These animals were also found to exhibit higher IgG2a levels greater cytokine (IFN-γ and IL-2) concentrations suggesting the generation of a strong Th1 type of immune response which is responsible for resolution of the disease.

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“…Recent first-line drugs against leishmaniasis include miltefosine, paromomycin, and liposomal amphotericin B, which present multiple shortcomings, such as resistance and side effects (35,36). Therefore, novel therapeutic approaches, particularly those aimed at exploring new horizons for the development of efficient antileishmanial molecules, are required (37)(38)(39).…”

Section: Discussionmentioning

confidence: 99%

Alkyl Galactofuranosides Strongly Interact with Leishmania donovani Membrane and Provide Antileishmanial Activity

Suleman

Gangneux

Legentil

et al. 2014

Antimicrob Agents Chemother

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fWe investigated the in vitro effects of four alkyl-galactofuranoside derivatives, i.e., octyl-␤-D-galactofuranoside (compound 1), 6-amino-␤-D-galactofuranoside (compound 2), 6-N-acetamido-␤-D-galactofuranoside (compound 3), and 6-azido-␤-D-galactofuranoside (compound 4), on Leishmania donovani. Their mechanism of action was explored using electron paramagnetic resonance spectroscopy (EPR) and nuclear magnetic resonance (NMR), and ultrastructural alterations were analyzed by transmission electron microscopy (TEM). Compound 1 showed the most promising effects by inhibiting promastigote growth at a 50% inhibitory concentration (IC 50 ) of 8.96 ؎ 2.5 M. All compounds exhibit low toxicity toward human macrophages. Compound 1 had a higher selectivity index than the molecule used for comparison, i.e., miltefosine (159.7 versus 37.9, respectively). EPR showed that compound 1 significantly reduced membrane fluidity compared to control promastigotes and to compound 3. The furanose ring was shown to support this effect, since the isomer galactopyranose had no effect on parasite membrane fluidity or growth. NMR showed a direct interaction of all compounds (greatest with compound 1, followed by compounds 2, 3, and 4, in descending order) with the promastigote membrane and with octyl-galactopyranose and octanol, providing evidence that the n-octyl chain was primarily involved in anchoring with the parasite membrane, followed by the putative crucial role of the furanose ring in the antileishmanial activity. A morphological analysis of compound 1-treated promastigotes by TEM revealed profound alterations in the parasite membrane and organelles, but this was not the case with compound 3. Quantification of annexin V binding by flow cytometry confirmed that compound 1 induced apoptosis in >90% of promastigotes. The effect of compound 1 was also assessed on intramacrophagic amastigotes and showed a reduction in amastigote growth associated with an increase of reactive oxygen species (ROS) production, thus validating its promising effect.

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Developments in Diagnosis and Antileishmanial Drugs

Cited by 50 publications

References 107 publications

New trends in the use of aminoglycosides

New trends in the use of aminoglycosides

To investigate the therapeutic potential of immunochemotherapy with cisplatin + 78 kDa + MPL‐A against Leishmania donovani in BALB/c mice

Alkyl Galactofuranosides Strongly Interact with Leishmania donovani Membrane and Provide Antileishmanial Activity

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