Advancement in leishmaniasis diagnosis and therapeutics: An update

Kumari, Diksha; Perveen, Summaya; Singh, Kuljit

doi:10.1016/j.ejphar.2021.174436

Cited by 42 publications

(40 citation statements)

References 178 publications

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“…The inhibition of any of the polyamine biosynthetic enzymes could potentially be circumvented by drug-resistance mechanisms, including a gene amplification event. Monotherapy with current antileishmanial drugs has demonstrated that the emergence of drug resistance is inevitable [ 13 , 15 , 217 , 218 , 219 , 220 ]. It is thus not surprising that combination therapy against leishmaniasis has recently received more attention [ 13 , 19 , 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…Pentavalent antimonials were introduced over six decades ago, and despite significant and severe side effects associated with their administration, and widespread resistance to their antileishmanial effects, they are still used as a first-line treatment in many countries. Their mechanism of action is complex, although the inhibition of trypanothione reductase and disruption of trypanothione metabolism appears to contribute significantly to their mode of action [ 13 , 15 ]. Amphotericin B, an antifungal medication, binds to ergosterol that is present in the membranes of Leishmania and related parasites, as well as susceptible fungi, but it is absent in the human host.…”

Section: Introduction To Leishmaniamentioning

confidence: 99%

“…Miltefosine is the only orally administered treatment approved for leishmaniasis. It appears to have multiple antileishmanial effects, including interference with phospholipid metabolism and the disruption of mitochondrial and acidocalcisome function [ 13 , 15 , 17 ]. Widespread use of miltefosine for treating leishmaniasis is limited by its teratogenic properties (the drug is contraindicated for use in pregnant women or in those that may become pregnant) and due to the emergence of drug-resistant strains [ 13 , 15 , 18 ].…”

Section: Introduction To Leishmaniamentioning

confidence: 99%

“…It appears to have multiple antileishmanial effects, including interference with phospholipid metabolism and the disruption of mitochondrial and acidocalcisome function [ 13 , 15 , 17 ]. Widespread use of miltefosine for treating leishmaniasis is limited by its teratogenic properties (the drug is contraindicated for use in pregnant women or in those that may become pregnant) and due to the emergence of drug-resistant strains [ 13 , 15 , 18 ]. Paromomycin, an aminoglycoside antibiotic, has been utilized with some success against VL and CL, but again, side effects such as hepatotoxicity occur and drug resistance have been demonstrated in the laboratory [ 13 , 15 ].…”

Section: Introduction To Leishmaniamentioning

confidence: 99%

“…Widespread use of miltefosine for treating leishmaniasis is limited by its teratogenic properties (the drug is contraindicated for use in pregnant women or in those that may become pregnant) and due to the emergence of drug-resistant strains [ 13 , 15 , 18 ]. Paromomycin, an aminoglycoside antibiotic, has been utilized with some success against VL and CL, but again, side effects such as hepatotoxicity occur and drug resistance have been demonstrated in the laboratory [ 13 , 15 ]. Pentamidine, an aromatic diamidine, is a second-line treatment that appears to act by accumulating in the mitochondria and binding to kinetoplastid DNA and topoisomerase II [ 13 ].…”

Section: Introduction To Leishmaniamentioning

confidence: 99%

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Polyamine Metabolism in Leishmania Parasites: A Promising Therapeutic Target

Carter¹,

Kawasaki²,

Nahata³

et al. 2022

Medical Sciences

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Parasites of the genus Leishmania cause a variety of devastating and often fatal diseases in humans and domestic animals worldwide. The need for new therapeutic strategies is urgent because no vaccine is available, and treatment options are limited due to a lack of specificity and the emergence of drug resistance. Polyamines are metabolites that play a central role in rapidly proliferating cells, and recent studies have highlighted their critical nature in Leishmania. Numerous studies using a variety of inhibitors as well as gene deletion mutants have elucidated the pathway and routes of transport, revealing unique aspects of polyamine metabolism in Leishmania parasites. These studies have also shed light on the significance of polyamines for parasite proliferation, infectivity, and host–parasite interactions. This comprehensive review article focuses on the main polyamine biosynthetic enzymes: ornithine decarboxylase, S-adenosylmethionine decarboxylase, and spermidine synthase, and it emphasizes recent discoveries that advance these enzymes as potential therapeutic targets against Leishmania parasites.

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