In vitro efficacy of synthesized artemisinin derivatives against Leishmania promastigotes

Aucamp, Janine; Zuma, Nonkululeko H.; N’Da, David D.

doi:10.1016/j.bmcl.2020.127581

Cited by 6 publications

(4 citation statements)

References 34 publications

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“…Resistance to artemisinin and DHA previously had been induced by exposing toxoplasma cultures to increasing concentrations of the ARTS. [87] Aucamp et al, [88] found that their newly synthesized ARTS were as much as 30-fold more potent against Leishmania promastigotes than the currently used commercial ARTS. However, the promastigote stage is not the one responsible for clinical leishmaniasis in humans or animals; drugs that act against a certain stage in the parasite lifecycle are not necessarily active against another stage.…”

Section: Parasitesmentioning

confidence: 99%

Applicability of Redirecting Artemisinins for New Targets

Golenser,

Hunt,

Birman

et al. 2023

Global Challenges

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Employing new therapeutic indications for drugs that are already approved for human use has obvious advantages, including reduced costs and timelines, because some routine steps of drug development and regulation are not required. This work concentrates on the redirection of artemisinins (ARTS) that already are approved for clinical use, or investigated, for malaria treatment. Several mechanisms of action are suggested for ARTS, among which only a few have been successfully examined in vivo, mainly the induction of oxidant stress and anti‐inflammatory effects. Despite these seemingly contradictory effects, ARTS are proposed for repurposing in treatment of inflammatory disorders and diverse types of diseases caused by viral, bacterial, fungal, and parasitic infections. When pathogens are treated the expected outcome is diminution of the causative agents and/or their inflammatory damage. In general, repurposing ARTS is successful in only a very few cases, specifically when a valid mechanism can be targeted using an additional therapeutic agent and appropriate drug delivery. Investigation of repurposing should include optimization of drug combinations followed by examination in relevant cell lines, organoids, and animal models, before moving to clinical trials.

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Section: Parasitesmentioning

confidence: 99%

Applicability of Redirecting Artemisinins for New Targets

Golenser,

Hunt,

Birman

et al. 2023

Global Challenges

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show abstract

“…28 Focusing on the latter, using commercially available DHA 16, the key intermediate aldehyde 19 was synthesized and reduced to the corresponding primary alcohol, which is esterified with various acyl chlorides obtaining the desired contracted artemisinin ester analogues 21a-d (Scheme 3). 29 It is worth mentioning that the stereochemistry of the new stereocenter, generated by the contraction of the sixmembered ring, is not controlled, being the products isolated as a mixture of epimers. The Leishmania antipromastigote activity of artemisinin analogues were studied in vitro in L. donovani and L. major stains.…”

Section: Natural Products and Analoguesmentioning

confidence: 99%

“…The Leishmania antipromastigote activity of artemisinin analogues were studied in vitro in L. donovani and L. major stains. 29 These molecules possessed high intrinsic activities (IC 50 ≤ 10 μM), without a toxic profile and a selective action (SI ≥ 10) toward Leishmania pathogens. Regarding L. donovani strain, the best result was achieved with the ester containing biphenyl moiety 21c (IC 50 = 2.80 μM), which was as much as 30-fold more potent than clinical artemisinins.…”

Section: Natural Products and Analoguesmentioning

confidence: 99%

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A recent update on new synthetic chiral compounds with antileishmanial activity

2022

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Parasitic diseases, including malaria, leishmaniasis, and trypanosomiasis, affect billions of people and are responsible for almost 500,000 deaths/year. In particular, leishmaniasis, a neglected tropical disease, is considered a global public health problem because current drugs have several drawbacks including to toxicity, high cost, and drug resistance, which result in a lack of effective and readily available therapies. Therefore, the synthesis of new, safe, and effective molecules still requires the attention of the scientific community. Moreover, it is well known that chirality plays a crucial role in the antiparasitic activity of molecules, driving the design of their synthesis. Therefore, in this review we report a recent update on new chiral compounds with promising antileishmanial activity, focusing on synthetic approaches. Where reported, in most cases the enantiopure compound has shown better potency against the protozoa than its enantiomer or corresponding racemic mixture.

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