How do the alkaloids emetine and homoharringtonine kill trypanosomes? An insight into their molecular modes of action

Krstin, Sonja; Mohamed, Tamer; Wang, Xiaojuan

doi:10.1016/j.phymed.2016.10.008

Cited by 19 publications

(19 citation statements)

References 31 publications

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“…Emetine is a drug with pleotropic properties that has been utilized as both an anti-protozoal and an emetic 25 – 27 . It is derived from the ipecac root and takes its name from its emetic properties.…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that emetine inhibits viral translation by blocking the 40S ribosomal protein S14 in host cells 37 , 38 . Studies have also indicated that emetine blocks HIV reverse transcriptase 39 , inhibits viral polymerases 9 , kills trypanosomes through DNA intercalation 27 , and suppresses human cytomegalovirus by disrupting the 40S ribosomal protein S14 26 . Furthermore, emetine has been shown to inhibit Dengue viral RNA synthesis 40 .…”

Section: Discussionmentioning

confidence: 99%

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Emetine inhibits Zika and Ebola virus infections through two molecular mechanisms: inhibiting viral replication and decreasing viral entry

et al. 2018

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The re-emergence of Zika virus (ZIKV) and Ebola virus (EBOV) poses serious and continued threats to the global public health. Effective therapeutics for these maladies is an unmet need. Here, we show that emetine, an anti-protozoal agent, potently inhibits ZIKV and EBOV infection with a low nanomolar half maximal inhibitory concentration (IC50) in vitro and potent activity in vivo. Two mechanisms of action for emetine are identified: the inhibition of ZIKV NS5 polymerase activity and disruption of lysosomal function. Emetine also inhibits EBOV entry. Cephaeline, a desmethyl analog of emetine, which may be better tolerated in patients than emetine, exhibits a similar efficacy against both ZIKV and EBOV infections. Hence, emetine and cephaeline offer pharmaceutical therapies against both ZIKV and EBOV infection.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Emetine inhibits Zika and Ebola virus infections through two molecular mechanisms: inhibiting viral replication and decreasing viral entry

et al. 2018

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“…Both norpurpureine (101) and purpureine (102) were isolated from Annona purpurea leaves. 61 nelumbinis.…”

Section: F I G U R E 4 the Chemical Structures Of Compounds 57−84mentioning

confidence: 99%

“…The isoquinoline ring in manzamine alkaloids is both attached to a β-carboline (9H-pyrido [ showed that 348 can be used as an emetic and expectorant, 156 and recently, its antiviral and anti-trypanosomes activities were proved. 102,157 In 2017, a new emetine isoquinoline alkaloid, 7′,10-dide-O-methylcephaeline (349), as well as the known 10-O-demethylprotoemetine (350) were identified and isolated from Ophiorrhiza nutans. 79 In 2018, two new alkaloids of this type, 8-hydroxytubulosine (351) and 9-demethyltubulosine (352), were isolated from A. longiflorum 80 ( Figure 18).…”

Section: Manzamine Alkaloidsmentioning

confidence: 99%

Biologically active isoquinoline alkaloids covering 2014–2018

Shang

Yang

Morris‐Natschke

et al. 2020

Medicinal Research Reviews

145

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Isoquinoline alkaloids, an important class of N-based heterocyclic compounds, have attracted considerable attention from researchers worldwide since the early 19th century. Over the past 200 years, many compounds from this class were isolated, and most of them and their analogs possess various bioactivities. In this review, we survey the updated literature on bioactive alkaloids and highlight research achievements of this alkaloid class during the period of 2014-2018. We reviewed over 400 molecules with a broad range of bioactivities, including antitumor, antidiabetic and its complications, antibacterial, antifungal, antiviral, antiparasitic, insecticidal, anti-inflammatory, antioxidant, neuroprotective, and other activities. This review should provide new indications or directions for the discovery of new and better drugs from the original naturally occurring isoquinoline alkaloids.

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“…Many FDA‐approved drugs, including those used for chemotherapy, have severe side effects that may prevent their use for other purposes. For example, emetine, better known as an active ingredient of ipecac syrup, binds ribosomes and inhibits a variety of disease‐causing protozoa . It has also been reported to selectively kill acute myeloid leukemia cells .…”

Section: Repurposing As a Path To New Drugsmentioning

confidence: 99%

Repurposing approved drugs on the pathway to novel therapies

Schein

2019

Medicinal Research Reviews

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The time and cost of developing new drugs have led many groups to limit their search for therapeutics to compounds that have previously been approved for human use. Many “repurposed” drugs, such as derivatives of thalidomide, antibiotics, and antivirals have had clinical success in treatment areas well beyond their original approved use. These include applications in treating antibiotic‐resistant organisms, viruses, cancers and to prevent burn scarring. The major theoretical justification for reusing approved drugs is that they have known modes of action and controllable side effects. Coadministering antibiotics with inhibitors of bacterial toxins or enzymes that mediate multidrug resistance can greatly enhance their activity. Drugs that control host cell pathways, including inflammation, tumor necrosis factor, interferons, and autophagy, can reduce the “cytokine storm” response to injury, control infection, and aid in cancer therapy. An active compound, even if previously approved for human use, will be a poor clinical candidate if it lacks specificity for the new target, has poor solubility or can cause serious side effects. Synergistic combinations can reduce the dosages of the individual components to lower reactivity. Preclinical analysis should take into account that severely ill patients with comorbidities will be more sensitive to side effects than healthy trial subjects. Once an active, approved drug has been identified, collaboration with medicinal chemists can aid in finding derivatives with better physicochemical properties, specificity, and efficacy, to provide novel therapies for cancers, emerging and rare diseases.

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How do the alkaloids emetine and homoharringtonine kill trypanosomes? An insight into their molecular modes of action

Cited by 19 publications

References 31 publications

Emetine inhibits Zika and Ebola virus infections through two molecular mechanisms: inhibiting viral replication and decreasing viral entry

Emetine inhibits Zika and Ebola virus infections through two molecular mechanisms: inhibiting viral replication and decreasing viral entry

Biologically active isoquinoline alkaloids covering 2014–2018

Repurposing approved drugs on the pathway to novel therapies

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