Modified quaternary ammonium salts as potential antimalarial agents

Basilico, Nicoletta; Migotto, Mara; Ilboudo, D.; Taramelli, Donatella; Stradi, Riccardo; Pini, Elena

doi:10.1016/j.bmc.2015.05.055

Cited by 17 publications

(7 citation statements)

References 23 publications

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“…The ammonium quaternary salts 47 and 48 were synthesized in an attempt to increase potency since quaternary ammonium salt derivatives were previously displayed as interesting antiplasmodial agents. [41] Both compounds displayed a drop of potency against gametocytes. Interestingly, benzyl-derivative 48 maintained its potency against the asexual forms of the parasite, but not against the gametocytes.…”

Section: Resultsmentioning

confidence: 99%

Antimalarial agents against both sexual and asexual parasites stages: structure-activity relationships and biological studies of the Malaria Box compound 1-[5-(4-bromo-2-chlorophenyl)furan-2-yl]-N-[(piperidin-4-yl)methyl]methanamine (MMV019918) and analogues

Vallone¹,

D’Alessandro²,

Brogi³

et al. 2018

European Journal of Medicinal Chemistry

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Therapies addressing multiple stages of Plasmodium falciparum life cycle are highly desirable for implementing malaria elimination strategies. MMV019918 (1, 1-[5-(4-bromo-2-chlorophenyl)furan-2-yl]-N-[(piperidin-4-yl)methyl]methanamine) was selected from the MMV Malaria Box for its dual activity against both asexual stages and gametocytes. In-depth structure-activity relationship studies and cytotoxicity evaluation led to the selection of 25 for further biological investigation. The potential transmission blocking activity of 25 versus P. falciparum was confirmed through the standard membrane-feeding assay. Both 1 and 25 significantly prolonged atrioventricular conduction time in Langendorff-isolated rat hearts, and showed inhibitory activity of Ba current through Ca1.2 channels. An in silico target-fishing study suggested the enzyme phosphoethanolamine methyltransferase (PfPMT) as a potential target. However, compound activity against PfPMT did not track with the antiplasmodial activity, suggesting the latter activity relies on a different molecular target. Nevertheless, 25 showed interesting activity against PfPMT, which could be an important starting point for the identification of more potent inhibitors active against both sexual and asexual stages of the parasite.

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Section: Resultsmentioning

confidence: 99%

Antimalarial agents against both sexual and asexual parasites stages: structure-activity relationships and biological studies of the Malaria Box compound 1-[5-(4-bromo-2-chlorophenyl)furan-2-yl]-N-[(piperidin-4-yl)methyl]methanamine (MMV019918) and analogues

Vallone¹,

D’Alessandro²,

Brogi³

et al. 2018

European Journal of Medicinal Chemistry

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“…Due to their toxic effect against algae, they can also be used on surfaces of swimming pools, fountains, and wooden boats . The antimalarial effect is also known . Moreover, above a particular minimum concentration, called the critical micellar concentration (CMC), these surfactant monomers form thermodynamically stable spherical aggregates in aqueous solutions known as micelles .…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Antimicrobial Effect and Lipophilicity‐Activity Dependence of Three Series of Dichained N‐Alkylammonium Salts

et al. 2019

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Quaternary ammonium salts belong to the group of cationic surfactants and their structure, especially the length of the alkyl chain, plays a significant role in its activity against various microorganisms. Globally, there is a growing need to develop novel compounds due to the increasing resistance of microorganisms to antimicrobial agents. Three series of quaternary ammonium compounds based on dichained N‐alkylammonium salts were synthesized with different carbon chain lengths (C8, C10, C12, C14, C16). These compounds were characterized with analytical methods and tested in vitro for antibacterial, antifungal, antiviral and antialgal activities. In addition, the determination of their critical micelle concentrations, lipophilicity and cytotoxicity were likewise performed to assess potential lipophilicity‐activity dependence. Almost all compounds showed a high efficacy against bacterial and fungal strains. Significant effects against Varicella zoster virus and algae were also noticed. Some of novel drugs outperformed standard benzalkonium salts. The expected trend of the correlation of an increase of cytotoxicity with the length of carbon chain was confirmed. These compounds show a higher potential as disinfectants rather than antiseptics due to their cytotoxic potential and low selectivity for microbes over mammalian cells.

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“…Parasite growth was examined spectrophotometrically (OD650) by measuring the activity of the parasite lactate dehydrogenase (pLDH), according to a modified version of the method of Makler [15,16]. The antiplasmodial activity is expressed as 50% inhibitory concentrations (IC 50 ) as mean ± standard deviation of at least three separate experiments performed in duplicate.…”

Section: Antiplasmodial Activitymentioning

confidence: 99%

In vitro antimalarial activity of selected medicinal plants native to Tigray region of Ethiopia

Tekulu¹,

D’Alessandro²,

Parapini³

et al. 2019

Preprint

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BackgroundVarious medicinal plants are used as alternative remedies for the management of malaria, an important infectious disease responsible for around 228 million cases and 405,000 deaths worldwide in 2018. The worsening of the disease is highly associated to an emergence of drug-resistant parasites. Hence, the search of new alternative antimalarial agents from traditionally used medicinal plants is the most viable approach. The current study was aimed to evaluate the in vitro antiplasmodial property of Aloe elegans, Aloe monticola, Capparis tomentosa, Hygrophila schulli and Tephrosia gracilipes extracts.Methods Leaf latexes were collected from Aloe elegans and Aloe monticola, whereas cold maceration with 70% ethanol was used to prepare extracts from roots of Capparis tomentosa and Tephrosia gracilipes , and leaves of Hygrophila schulli . The antiplasmodial activity of the extracts against asexual and gametocyte stages was tested using parasite lactate dehydrogenase assay and luciferase assay, respectively. Cell cytotoxicity was assessed on human microvascular endothelial cells by the MTT assayResults Of the five selected medicinal plants, leaf latex of Aloe monticola showed the best activity against both asexual stages and stage V gametocytes of Plasmodium falciparum . The leaf latex of Aloe elegans and ethanolic extract of Hygrophila schulli leaves also showed antiplasmodial property against asexual stages. On the contrary, the roots of Capparis tomentosa and Tephrosa gracilipes were inactive.Conclusion Findings of this study may partly support the acclaimed traditional use of the leaves latexes of both Aloe elegans and Aloe monticola and the ethanolic extract of Hygrophila schulli leaves for the management of mild to moderate malaria.

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Modified quaternary ammonium salts as potential antimalarial agents

Cited by 17 publications

References 23 publications

Antimalarial agents against both sexual and asexual parasites stages: structure-activity relationships and biological studies of the Malaria Box compound 1-[5-(4-bromo-2-chlorophenyl)furan-2-yl]-N-[(piperidin-4-yl)methyl]methanamine (MMV019918) and analogues

Antimalarial agents against both sexual and asexual parasites stages: structure-activity relationships and biological studies of the Malaria Box compound 1-[5-(4-bromo-2-chlorophenyl)furan-2-yl]-N-[(piperidin-4-yl)methyl]methanamine (MMV019918) and analogues

Synthesis, Antimicrobial Effect and Lipophilicity‐Activity Dependence of Three Series of Dichained N‐Alkylammonium Salts

In vitro antimalarial activity of selected medicinal plants native to Tigray region of Ethiopia

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