Publications of Michel Frederich
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See detailPolyhydroxybenzoic acid derivatives as potential new antimalarial agents
Degotte, Gilles ULiege; Pirotte, Bernard ULiege; Frederich, Michel ULiege et al

in Archiv der Pharmazie und Berichte der Deutschen Pharmazeutischen Gesellschaft (in press)

With more than 200 million cases and 400,000 related deaths, malaria remains one of the deadliest infectious diseases of 2021. Unfortunately, despite the availability of efficient treatments, we have ... [more ▼]

With more than 200 million cases and 400,000 related deaths, malaria remains one of the deadliest infectious diseases of 2021. Unfortunately, despite the availability of efficient treatments, we have observed an increase in people infected with malaria since 2015 (from 211 million in 2015 to 229 million in 2019). This trend could partially be due to the development of resistance to all the current drugs. Therefore, there is an urgent need for new alternatives. We have, thus, selected common natural scaffolds, polyhydroxybenzoic acids, and synthesized a library of derivatives to better under- stand the structure–activity relationships explaining their antiplasmodial effect. Only gallic acid derivatives showed a noticeable potential for furtherQ3 developments. Indeed, they showed a selective inhibitory effect on Plasmodium (IC50 ~20 μM, SI > 5) often associated with interesting water solubility. Moreover, this has confirmed the critical importance of free phenolic functions (pyrogallol moiety) for the antimalarial effect. Methyl 4-benzoxy-3,5-dihydroxybenzoate (39) has, for the first time, been recognized as a potential lead for future research because of its marked inhibitory activity against Plasmodium falciparum and its significant hydrosolubility (3.72 mM). [less ▲]

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See detailCould Bis-THIQ compounds inhibit plasmodial growth through SK channel interaction ?
Taouba, Hossein ULiege; Vitello, Romain ULiege; Lumb, Jean-Philip et al

Poster (2021, May 26)

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See detailIn Vitro Antiplasmodial and Cytotoxic Activities of Compounds from the Roots of Eriosema montanum Baker f. (Fabaceae)
Tomani, Jean Claude Didelot; Bonnet, Olivier ULiege; Nyirimigabo, Alain et al

in Molecules (2021), 26(9), 2795

Malaria remains one of the leading causes of death in sub-Saharan Africa, ranked in thetop three infectious diseases in the world. Plants of theEriosemagenus have been reported to beused for the treatment ... [more ▼]

Malaria remains one of the leading causes of death in sub-Saharan Africa, ranked in thetop three infectious diseases in the world. Plants of theEriosemagenus have been reported to beused for the treatment of this disease, but scientific evidence is still missing for some of them. Inthe present study, thein vitroantiplasmodial activity of the crude extract and compounds fromEriosema montanum Baker f.roots were tested against the 3D7 strain ofPlasmodium falciparumandrevealed using the SYBR Green, a DNA intercalating compound. The cytotoxicity effect of thecompounds on a human cancer cell line (THP-1) was assessed to determine their selectivity index.It was found that the crude extract of the plant displayed a significant antiplasmodial activitywith anIC50(μg/mL) = 17.68±4.030and a cytotoxic activity with a CC50(μg/mL) = 101.5±12.6,corresponding to a selective antiplasmodial activity of 5.7. Bioactivity-guided isolation of the majorcompounds of the roots’ crude extract afforded seven compounds, including genistein, genistin andeucomic acid. Under our experimental conditions, using Artemisinin as a positive control, eucomicacid showed the best inhibitory activity against theP. falciparum3D7, a well-known chloroquine-sensitive strain. The present results provide a referential basis to support the traditional use ofEriosemaspecies in the treatment of malaria. [less ▲]

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See detailOverview of natural antiplasmodials from the last decade to inspire medicinal chemistry
Degotte, Gilles ULiege; Pirotte, Bernard ULiege; Francotte, Pierre ULiege et al

in Current Medicinal Chemistry (2021)

Background: Despite the major advances in the fight against this parasitic disease, malaria remains a major cause of concerns in 2020. This infection, mainly due to Plasmodium falciparum, causes every ... [more ▼]

Background: Despite the major advances in the fight against this parasitic disease, malaria remains a major cause of concerns in 2020. This infection, mainly due to Plasmodium falciparum, causes every year more than 200 million of cases and hundreds of thousands of deaths in developing regions, mostly in Africa. The last statistics show an increase of cases for the third consecutive year, from 211 million in 2015, it has reached 229 million in 2019. This trend could be partially explained by the appearance of resistances to all the used antimalarials, even to artemisinin. Thus, the design of new anti-Plasmodium compounds is an urgent need. For thousands of years, nature has offered to humans the medicines to cure their diseases or the inspiration for development of new active principles. It seems then logical to explore the natural sources to find new molecules to treat this parasitosis. Method: Therefore, this review reports and analyzes the extracts (plants, bacteria, sponges, fungi) and the corresponding isolated compounds showing antiplasmodial properties between 2013 and 2019. Results & Conclusion: Nature remains a major source of active compounds. Indeed, 648 molecules from various origins, mostly plants, have been reported for their inhibitory effect on Plasmodium falciparum. Among them, 188 scaffolds were defined as highly active with IC50 ≤ 5 µM and have been reported here in details. Moreover, the most active compounds showed a large variety of structures: flavonoids, triterpenes, alkaloids... Therefore, these compounds could be an interesting source of inspiration for medicinal chemists. May-be several of these molecules should become the next leads for malaria treatment. [less ▲]

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See detailA new isoquinoline and ceramide from the stem barks of Discoglypremna caloneura (Pax) Prain (Euphorbiaceae) with antiproteinase and cytotoxic activities.
Toukam, Paul Djouonzo; Kom, Christelle Wayoue; Tchamgoué, Armelle Deutou et al

in Natural Product Research (2021)

Two new compounds, an isoquinoline (1) and caloneuramide (2), a ceramide were isolated from the stem bark of Discoglypremna caloneura together with seven known compounds namely aurantiamide acetate (3 ... [more ▼]

Two new compounds, an isoquinoline (1) and caloneuramide (2), a ceramide were isolated from the stem bark of Discoglypremna caloneura together with seven known compounds namely aurantiamide acetate (3), acetylaleuritolic acid (4), 3α-hydroxylaleuritolic acid 2α-p-hydroxybenzoate (5), mixture of stigmasterol (6) and β-sitosterol (7), mixture of 7-oxo-stigmasterol (8) and 7-oxo-β-sitosterol (9). Their structures were determined based on data from literature and spectroscopic methods. Derivatization reactions on the isoquinoline led to two new compounds, the methylated (10) and acetylated (11) derivatives. Some compounds and extracts were evaluated for their cytotoxic and antiproteinase activity. Antiproteinase effect of compounds 1, 10 and 11 exhibited IC(50) values of 10.77, 1.19 and 3.61 μg/mL respectively; significantly low compared to the standard drug, acetyl salicylic acid (IC(50) = 20.28 μg/mL). Ethyl acetate and methanol extract exhibited moderate cytotoxicity activity on Chang liver cells with CC(50) values of 167.90 ± 2.20 and 106.30 ± 2.03 μg/mL compared to the reference drug cucurmin (CC(50) = 11.05 ± 1.04 μg/mL). [less ▲]

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See detailPhytochemical investigation and biological activities from Lantana rhodesiensis Moldenke.
Nea, Fatimata ULiege; Bitchi, Boni Michel; Genva, Manon ULiege et al

Poster (2021, January 15)

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See detailPhytochemical investigation and biological activities of Lantana rhodesiensis
Nea, Fatimata ULiege; Bitchi, Michel Boni; Genva, Manon ULiege et al

in Molecules (2021), 26(4), 846

Lantana rhodesiensis Moldenke is a plant widely used to treat diseases, such as rheumatism, diabetes, and malaria in traditional medicine. To better understand the traditional uses of this plant, a ... [more ▼]

Lantana rhodesiensis Moldenke is a plant widely used to treat diseases, such as rheumatism, diabetes, and malaria in traditional medicine. To better understand the traditional uses of this plant, a phytochemical study was undertaken, revealing a higher proportion of polyphenols, including flavonoids in L. rhodesiensis leaf extract and moderate proportion in stem and root extracts. The antioxidant activity of the extracts was also determined using three different assays: the radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity, the FRAP method (Ferric-reducing antioxidant power) and the β-carotene bleaching test. The anti-malarial activity of each extract was also evaluated using asexual erythrocyte stages of Plasmodium falciparum, chloroquine-sensitive strain 3D7. The results showed that the leaf extract exhibited higher antioxidant and anti-malarial activities in comparison with the stem and root extracts, probably due to the presence of higher quantities of polyphenols including flavonoids in the leaves. A positive linear correlation was established between the phenolic compound content (total polyphenols including flavonoids and tannins; and total flavonoids) and the antioxidant activity of all extracts. Furthermore, four flavones were isolated from leaf dichloromethane and ethyl acetate fractions: a new flavone named rhodescine (5,6,3’,5’-tetrahydroxy-7,4’-dimethoxyflavone) (1), 5-hydroxy-6,7,3’,4’,5’-pentamethoxyflavone (2), 5-hydroxy-6,7,3′,4′-tetramethoxyflavone (3), and 5,6,3’-trihydroxy-7,4’-dimethoxyflavone (4). Their structures were elucidated by 1H, 13C NMR, COSY, HSQC, HMBC, and MS-EI spectral methods. Aside from compound 2, all other molecules were described for the first time in this plant species. [less ▲]

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See detailPentas longiflora Oliv. (Rubiaceae), a plant used in the treatment of Pityriasis Versicolor in Rwanda: Chemical composition and standardization of leaves and roots
Kagisha, Vedaste ULiege; Marini Djang'Eing'A, Roland ULiege; Muganga, Raymond et al

in Fitoterapia (2021), 153

In Rwanda, the roots of Pentas longiflora Oliv. (Rubiaceae) have been used for a long time to treat Pityriasis versicolor. However, many people reported the use of leaves instead of roots. This research ... [more ▼]

In Rwanda, the roots of Pentas longiflora Oliv. (Rubiaceae) have been used for a long time to treat Pityriasis versicolor. However, many people reported the use of leaves instead of roots. This research was conducted to compare the phytochemical composition and establish chromatographic methods for the standardization of roots and leaves extracts of P. longiflora. During this process, three new pentalongin glycosides (pentalonginoside A, pentalonginoside B, and pentalonginoside C) and two known glycosides of the same type (harounoside and clarinoside), as well as rutin, luteolin-7-rutinoside were isolated from methanol extract of leaves. In addition, pentalongin and psychorubrin, previously isolated from ethylacetate roots extract, were also identified in Pentas longiflora ethylacetate leaves extract. The presence of the antifungal compound pentalongin in leaves may explain the traditional use of leaves in the treatment of Pytiriasis versicolor. Furthermore, harounoside, psychorubrin, and pentalongin were selected as markers for HPLC fingerprints of MeOH extract. The accuracy and risk profile demonstrated the reliability of the validated method. In general, considerable variations of concentration in plant metabolites, including pentalongin, were observed between samples from different sites. The content in pentalongin (expressed as juglone) in collected samples ranged between 1.7 and 70.0 mg/100 g. The highest concentration (70.0 ± 17 mg/100 g) was registered in the cultivated samples from Mukoni. This important variation of pentalongin concentrations according to sampling sites, shows that in order to guarantee equivalent efficacy, finished products with P. longiflora should be standardized based on their pentalongin content. [less ▲]

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See detailAntiplasmodial and antileishmanial inhibitory activity of triterpenes and steroidal alkaloid from the leaves of Funtumia elastica (Preuss) Stapf (Apocynaceae)
Ma'mag, Larissa Kom; Zintchem, Auguste Abouem A.; Théodora, Kopa Kowa et al

in Fitoterapia (2021)

The phytochemical study of leaves of Funtumia elastica led to the isolation of three undescribed ursane derivatives, funtumic acids A, B and C (1–3), as well as one steroidal alkaloid, elasticine (4) and ... [more ▼]

The phytochemical study of leaves of Funtumia elastica led to the isolation of three undescribed ursane derivatives, funtumic acids A, B and C (1–3), as well as one steroidal alkaloid, elasticine (4) and five other known compounds (5–9). Their structures were elucidated on the basis of NMR, MS, IR, UV spectroscopic data as well as by comparison with the literature. The compound 5-hydroxypyridine-3-carboxamide (9) was isolated for the first time from the Apocynaceae family. All the isolated compounds were evaluated for their antiparasitic effects against 3D7 and Dd2 strains of Plasmodium falciparum and promastigotes of Leishmania donovani (MHOM/SD/62/1S). Compounds 1–4 possessed good in vitro antimalarial activities against CQR Dd2 with IC50 values ranging from 4.68 to 5.36 μg/mL and moderate on CQS 3D7. Only compounds 1 and 2 showed leishmanicidal activities with IC50 values ranging between 10.49 and 13.21 μg/mL. In addition, crude extract exhibited potent antiplasmodial (IC50 0.91 and 3.12 μg/mL) and antileishmanial (IC50 3.32 μg/mL) activities, thus demonstrating their potential synergistic action. [less ▲]

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See detailFROM MEDICINAL PLANT TO THE IMPROVED HERBAL MEDICINE
Kagisha, Vedaste ULiege; Frederich, Michel ULiege; muganga, Raymond et al

Poster (2020, December 09)

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See detailHPLC-UV method for standardization of Neorautanenia mitis, an African plant used in an anti-scabies ointment
Kagisha, Vedaste ULiege; Muganga, Raymond; Marini Djang'Eing'A, Roland ULiege et al

Scientific conference (2020, September 27)

An HPLC-UV method for standardization of the methanol-soluble extracts from tubers of Neorautanenia mitis (A.Rich.) Verdc., Leguminosae, harvested during different periods and from different sites, is ... [more ▼]

An HPLC-UV method for standardization of the methanol-soluble extracts from tubers of Neorautanenia mitis (A.Rich.) Verdc., Leguminosae, harvested during different periods and from different sites, is described. The chemical fingerprint was established with six identified markers using LC-ESI (+)-MS/MS, including rotenone; the total error was used as validation criterion, the accuracy and risk profiles demonstrated the reliability of the method. The study verified that the major degradation product of rotenone in methanol is dehydrorotenone. The detection range of rotenone was between 40 and 400 µg/ml. The collected samples contained 868-5732 µg/g of rotenone. The concentrations of rotenone in the wild samples from the Ngoma site (5167 ± 565 µg/g) were higher than those registered in the samples from the other sites. No significant differences were observed among the remaining sampling sites, and most of the rotenone was located in the inner part of the tubers (2165 ± 1051 µg/g) when compared to that in their peels (961 ± 320 µg/g). [less ▲]

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See detailIdentification of a proanthocyanidin from Litchi chinensis Sonn. root with anti-tyrosinase and antioxidant activity
Saive, Matthew ULiege; Genva, Manon ULiege; Istasse, Thibaut ULiege et al

in Biomolecules (2020), 10(9), 1347

This work follows an ethnobotanical study that took place in the island of Mayotte (France), which pointed out the potential properties of Litchi chinensis Sonn. roots when used to enhance skin health and ... [more ▼]

This work follows an ethnobotanical study that took place in the island of Mayotte (France), which pointed out the potential properties of Litchi chinensis Sonn. roots when used to enhance skin health and appearance. Through in vitro testing of a crude methanolic extract, high anti-tyrosinase (skin whitening e ect) and antioxidant activities (skin soothing e ect) could be measured. HPLC successive bio-guided fractionation steps allowed the purification of one of the compounds responsible for the biological activities. The isolated compound was characterized by UV, IR, MS and 2D-NMR, revealing, for the first time in Litchi chinensis Sonn. roots, an A-type proanthocyanidin and thus revealing a consensus among the traditional use shown by the ethnobotanical study, in vitro biological activities and chemical characterization. [less ▲]

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See detailHow the Genus Eusirus amphipods evolved and speciated in the Antarctic
Salabao, Louraine ULiege; Frederich, Michel ULiege; Lepoint, Gilles ULiege et al

Conference (2020, August)

Antarctica has been subjected to different climatic changes in the past requiring the marine fauna to either adapt to novel environmental conditions, migrate to better conditions or become extinct ... [more ▼]

Antarctica has been subjected to different climatic changes in the past requiring the marine fauna to either adapt to novel environmental conditions, migrate to better conditions or become extinct. Currently, warming of Antarctica is happening at an unprecedented rate. Understanding how these organisms have managed to survive in the past will thus allow us to predict their possible responses to future climate changes. Here, the amphipod Genus Eusirus will be used as model organisms since these amphipods are very diverse and knowledge on their ecology and biogeography is still very limited. In this study, molecular, morphological and ecological data of Eusirus will be collected. Because no reference genome exists for this group, we will use a Next generation sequencing approach to obtain the complete mitochondrial genome (mitogenome) of these amphipods. Draft mitogenomes have been assembled and annotated from skim sequencing for two Eusirus species. From these mitogenomes, we designed primers for long-range PCRs to amplify the entire mitogenome in several pieces. Complete mitogenomes will allow us to estimate genetic divergence amongst different species and check for specific temperature adaptations of mitochondrial genes. The obtained mitogenome data will also provide better supported phylogenies for reconstructing evolutionary history of Eusirus. In order to get a better understanding of adaptive and/or non-adaptive processes which led to the current diversity of Eusirus amphipods, we will explore how morphological and ecological diversity are partitioned along the resulting phylogeny, concurrently with potential changes in lineage diversification through time. [less ▲]

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See detailHPLC-UV Method for Standardization of Neorautanenia mitis, an African Plant Used in an Anti-Scabies Ointment
Kagisha, Vedaste ULiege; Frederich, Michel ULiege; Ledoux, Allison ULiege et al

in Revista Brasileira de Farmacognosia (2020), 30(4), 582-587

An HPLC-UV method for standardization of the methanol-soluble extracts from tubers of Neorautanenia mitis (A.Rich.) Verdc., Fabaceae, harvested during different periods and from different sites, is ... [more ▼]

An HPLC-UV method for standardization of the methanol-soluble extracts from tubers of Neorautanenia mitis (A.Rich.) Verdc., Fabaceae, harvested during different periods and from different sites, is described. The chemical fingerprint was established with six identified markers using LC-ESI (+)-MS/MS, including rotenone; the total error was used as validation criterion, the accuracy and risk profiles demonstrated the reliability of the method. The study verified that the major degradation product of rotenone in methanol is dehydrorotenone. The detection range of rotenone was between 40 and 400 μg/ml. The collected samples contained 868–5732 μg/g of rotenone. The concentrations of rotenone in the wild samples from the Ngoma site (5167 ± 565 μg/g) were higher than those registered in the samples from the other sites. No significant differences were observed among the remaining sampling sites, and most of the rotenone was located in the inner part of the tubers (2165 ± 1051 μg/g) when compared with that in their peels (961 ± 320 μg/g). [less ▲]

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See detailHeparin-Coated Liposomes Improve Antiplasmodial Activity and Reduce the Toxicity of Poupartone B
Ledoux, Allison ULiege; Coelho Cristino Mamede, Lucia Cristina ULiege; Palazzo, Claudio et al

in Planta Medica International Open (2020), 7(e), 7380

Poupartone B is an alkyl cyclohexenone derivative isolated from Poupartia borbonica. This compound demonstrated promising antimalarial activity (IC50 < 1 μg/mL), however, it was not de- void of toxicity ... [more ▼]

Poupartone B is an alkyl cyclohexenone derivative isolated from Poupartia borbonica. This compound demonstrated promising antimalarial activity (IC50 < 1 μg/mL), however, it was not de- void of toxicity. Thus, to reduce the adverse side effects of this natural bioactive molecule, a delivery strategy involving a na- nostructure was formulated. Additionally, poupartone B-load- ed liposomes were coated with heparin, a glycosaminoglycan that is known to target proteins on the surface of Plasmodium falciparum-infected red blood cells. The quantification of the compound in the formulation was performed by HPLC-DAD, while heparin was quantitated by 1H NMR spectroscopy. The liposomes’ antiplasmodial activity was tested on artemisinin- resistant P. falciparum isolate, and toxicity was evaluated on human HeLa cells and zebrafish embryos. Throughout this re- search, the formulation demonstrated higher antiplasmodial activities against both P. falciparum strains and a significant decrease of in vitro toxicity. The formulation improved the se- lectivity index 2 times in vitro and proved to be 3 times less toxic than the compound alone in the zebrafish embryo acute toxicity test. Hence, the use of this strategy to deliver natural products in Plasmodium-infected cells, particularly those with a narrow therapeutic margin, is proposed. [less ▲]

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