Journal ArticleDOI
Chemotherapy of leishmaniasis: past, present and future.
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TLDR
The present review describes the current understanding of different drugs against leishmaniasis, their chemistry, mode of action and the mechanism of resistance in the parasite.Abstract:
Leishmaniasis is a parasitic disease caused by hemoflagellate, Leishmania spp. The parasite is transmitted by the bite of an infected female phlebotomine sandfly. The disease is prevalent throughout the world and in at least 88 countries. Nearly 25 compounds are reported to have anti-leishmanial effects but not all are in use. The pentavalent antimony compounds have remained mainstay for nearly 75 years. Pentavalent antimony is a prodrug that is reduced by glutathione to active trivalent species catalyzed by thiol-dependent-reductase. However, emergence of resistance led to the use of other compounds -amphotericin B, pentamidine, paromomycin, allopurinol etc. Amphotericin B, an antifungal macrolide polyene is characterized by the hydrophilic polyhydroxyl and hydrophobic polyene faces on it long axis. Presently, it is the only drug with highest cure rate. It acts on membrane sterols resulting in parasite cell lysis. Its lipid formulations have been developed to minimize side effects. Other anti-fungals like ketoconazole, fluconazole and terbinafine are found less effective. Recently, anticancer alkylphosphocholines have been found most effective oral compounds. These act as membrane synthetic ether-lipid analogues, and consist of alkyl chains in the lipid portions. Most promising of these are miltefosine (hexadecylphosphocholine), edelfosine (ET-18-OCH3) and ilmofosine (BM 41.440). However, the recent focus has been on identifying newer therapeutic targets in the parasite such as DNA topoisomerases. The present review describes the current understanding of different drugs against leishmaniasis, their chemistry, mode of action and the mechanism of resistance in the parasite. Future perspectives in the area of new anti-leishmanial drug targets are also enumerated. However, due to the vastness of the topic main emphasis is given on visceral leishmaniasis.read more
Citations
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Journal ArticleDOI
Use of antimony in the treatment of leishmaniasis: current status and future directions.
TL;DR: It has been shown that some of the peroxovanadium compounds have Sb(V)-resistance modifying ability in experimental infection with Sb (V) resistant Leishmania donovani isolates in murine model, and vanadium compounds may be used in combination with S b(V) in the treatment of Sb.(V) resistance cases of kala-azar.
Journal ArticleDOI
Proteomic analysis of the secretome of Leishmania donovani
J Maxwell Silverman,J Maxwell Silverman,Simon K Chan,Simon K Chan,Dale P Robinson,Dale P Robinson,Dennis M. Dwyer,Devki Nandan,Devki Nandan,Leonard J. Foster,Leonard J. Foster,Neil E. Reiner,Neil E. Reiner +12 more
TL;DR: This analysis shows that protein secretion by L. donovani is a heterogeneous process that is unlikely to be determined by a classical amino-terminal secretion signal, and as an alternative, L.Donovani appears to use multiple nonclassical secretion pathways, including the release of exosome-like microvesicles.
Journal ArticleDOI
Pharmaceutical and medicinal significance of sulfur (SVI)-Containing motifs for drug discovery: A critical review.
TL;DR: A comprehensive review highlights the recent developments of sulfonyl or sulfonamides based compounds in huge range of therapeutic applications such as antimicrobial, anti-inflammatory, antiviral, anticonvulsant, antitubercular, antidiabetic, antileishmanial, carbonic anhydrase, antimalarial, anticancer and other medicinal agents.
Journal ArticleDOI
Recent developments in drug discovery for leishmaniasis and human African trypanosomiasis.
Advait Nagle,Shilpi Khare,Arun Kumar,Frantisek Supek,Andriy Buchynskyy,Casey J. N. Mathison,Naveen Kumar Chennamaneni,Nagendar Pendem,Frederick S. Buckner,Michael H. Gelb,Valentina Molteni +10 more
TL;DR: The disease history and parasite biology is described followed by a summary of the currently available treatments and, finally, review reports of novel small molecules with antileishmanial activity.
Journal ArticleDOI
Structural basis of human CYP51 inhibition by antifungal azoles.
TL;DR: Comparison of the azole-bound structures provides insight into the relative binding affinities of human and bacterial P450 enzymes to ketoconazole and fluconazole, which can be useful for the rational design of antifungal compounds and specific modulators of human CYP51.
References
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Journal ArticleDOI
Aminoglycosides: Activity and Resistance
TL;DR: Aminoglycosides are highly potent, broad-spectrum antibiotics with many desirable properties for the treatment of life-threatening infections and have a history marked by the successive introduction of a series of milestone compounds.
Journal ArticleDOI
Oral Miltefosine for Indian Visceral Leishmaniasis
Shyam Sundar,T. K. Jha,Thakur Cp,Juergen Engel,Herbert Sindermann,Christina Fischer,Klaus Junge,Anthony Bryceson,Jonathan Berman +8 more
TL;DR: Oral miltefosine is an effective and safe treatment for Indian visceral leishmaniasis and may also be helpful in regions where parasites are resistant to current agents.
Journal Article
Bioactivities of chalcones.
TL;DR: In this article, the authors outline the different bioactivities of a variety of chalcones and describe the cytotoxic, anticancer, chemopreventative and mutagenic properties of a number of CHs followed by an account of various CHs as antimicrobial agents.
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