In vitro anti-parasitic activity and mechanism of β-carboline derivatives isolated from the extracellular product of Salinivibrio proteolyticus strain YCSC6

We have developed a robust, fully automated anti-parasitic drug-screening method that selects compounds specifically targeting parasite enzymes and not their host counterparts, thus allowing the early elimination of compounds with potential side effects. Our yeast system permits multiple parasite targets to be assayed in parallel owing to the strains’ expression of different fluorescent proteins. A strain expressing the human target is included in the multiplexed screen to exclude compounds that do not discriminate between host and parasite enzymes. This form of assay has the advantages of using known targets and not requiring the in vitro culture of parasites. We performed automated screens for inhibitors of parasite dihydrofolate reductases, N -myristoyltransferases and phosphoglycerate kinases, finding specific inhibitors of parasite targets. We found that our ‘hits’ have significant structural similarities to compounds with in vitro anti-parasitic activity, validating our screens and suggesting targets for hits identified in parasite-based assays. Finally, we demonstrate a 60 per cent success rate for our hit compounds in killing or severely inhibiting the growth of Trypanosoma brucei , the causative agent of African sleeping sickness.

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Anti-plasmodial Effects of Zanthoxylum zanthoxyloides

Planta Medica ◽

10.1055/a-0973-0067 ◽

2019 ◽

Vol 85 (13) ◽

pp. 1073-1079 ◽

Cited By ~ 1

Author(s):

Christopher Dean Goodman ◽

An Thuy Hoang ◽

Drissa Diallo ◽

Karl Egil Malterud ◽

Geoffrey I. McFadden ◽

...

Keyword(s):

Brine Shrimp ◽

Methanol Extract ◽

Stem Bark ◽

Artemia Salina ◽

Root Bark ◽

Ic50 Values ◽

Zanthoxylum Zanthoxyloides ◽

Parasitic Activity ◽

Resistant Strains

Abstract Zanthoxylum zanthoxyloides, syn. Fagara zanthoxyloides, is a tree growing in West Africa and is used in traditional medicine against a variety of diseases, including malaria. In the work reported here, root bark and stem bark extracts of this tree, as well as compounds isolated from the extracts, have been investigated for activity in vitro against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. In addition, toxicity against nauplii of the brine shrimp Artemia salina has been studied. Dichloromethane extracts of the root bark and stem bark, and a methanol extract of the stem bark, showed anti-parasitic activity towards chloroquine-sensitive as well as chloroquine-resistant P. falciparum, with IC50 values between 1 and 10 µg/mL. Among the isolated compounds, bis-dihydrochelerythrinyl ether, buesgenine, chelerythrine, γ-fagarine, skimmianine, and pellitorine were the most active, with IC50 values of less than 5 µg/mL. The dichloromethane extracts were toxic to brine shrimp nauplii, with LC50 values of less than 1 µg/mL. Methanol extracts were much less toxic (LC50 between 50 and 100 µg/mL). Among the isolated substances, bis-dihydrochelethrinyl ether was the most toxic (LC50 ca. 2 µg/mL).

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In vitro screening of 51 birdsfoot trefoil (Lotus corniculatus L.; Fabaceae) strains for anti-parasitic effects against Haemonchus contortus

Parasitology ◽

10.1017/s0031182018002214 ◽

2019 ◽

Vol 146 (6) ◽

pp. 828-836 ◽

Cited By ~ 2

Author(s):

Carly D. Barone ◽

Anne M. Zajac ◽

Sarah M. Ferguson ◽

Rebecca N. Brown ◽

Jess D. Reed ◽

...

Keyword(s):

Haemonchus Contortus ◽

Small Ruminants ◽

Secondary Compounds ◽

Lotus Corniculatus ◽

Birdsfoot Trefoil ◽

Aqueous Extracts ◽

Egg Hatching ◽

Parasitic Activity ◽

Parasitic Effects

AbstractSecondary plant compounds have shown bioactivity against multi-drug resistant Haemonchus contortus in small ruminants. This study screened 51 strains of birdsfoot trefoil (BFT, Lotus corniculatus) crude aqueous extracts (BFT-AqE) for anti-parasitic activity in vitro against egg hatching, and of those 51 strains, 13 were selected for further testing of motility of first (L1) and third stage (L3) larvae, and exsheathment of L3. Proanthocyanidin content ranged between 1.4 and 63.8 mg PAC g−1 powder across the 51 BFT strains. When tested against egg hatching, 21 of the 51 aqueous extracts had an EC50 of 1–2 mg powder mL−1, 70% of the strains were >90% efficacious at 6 mg powder mL−1 and 11 of the strains were 100% efficacious at 3 mg powder mL−1 BFT-AqE. Across the 13 strains tested against L3, efficacy ranged from 0 to 75% exsheathment inhibition, and 17 to 92% L3 motility inhibition at a concentration of 25 mg powder mL−1 BFT-AqE. There was no correlation between the PAC content of BFT powders and the anti-parasitic activity of aqueous extracts, therefore other secondary compounds may have contributed to the observed anti-parasitic effects. Further testing of BFT using bioactivity-driven fractionation and screening of BFT populations for the identified anti-parasitic compounds is needed.

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In vitro anti-parasitic activity of Cyclosporin A analogs on Trypanosoma cruzi

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2004.07.003 ◽

2004 ◽

Vol 14 (18) ◽

pp. 4633-4637 ◽

Cited By ~ 23

Author(s):

Jacqueline Búa ◽

Andrés M. Ruiz ◽

Mariana Potenza ◽

Laura E. Fichera

Keyword(s):

Trypanosoma Cruzi ◽

Cyclosporin A ◽

Parasitic Activity

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Anti-parasitic activity of nano Citrullus colocynthis and nano Capparis spinose against Trichomonas vaginalis in vitro

Journal of Parasitic Diseases ◽

10.1007/s12639-021-01371-4 ◽

2021 ◽

Author(s):

Musafer H. Al-Ardi

Keyword(s):

Trichomonas Vaginalis ◽

Citrullus Colocynthis ◽

Parasitic Activity

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Efficacy of Capparis spinosa Linn Leaf and Fruit Extracts on Giardia Lambia Cysts In vitro

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i29a31582 ◽

2021 ◽

pp. 224-230

Author(s):

Aram Mohamadian ◽

Asad Mirzaei ◽

Naser Abbasi ◽

Razi Naserifar ◽

Jalil Feizi ◽

...

Keyword(s):

Giardia Lamblia ◽

Intestinal Parasites ◽

Lethal Effect ◽

Giardia Cyst ◽

First Line ◽

Leaf Extracts ◽

Fruit Extract ◽

Capparis Spinosa ◽

Parasitic Activity

Aims: Giardia lamblia (G. lamblia) is one of the most common intestinal parasites worldwide. There are some side effects and the reports of parasite resistance to metronidazole as the first line treatment of giardiasis. Therefore, it is essential to discover an effect and safe drug to treat giardiasis. Methodology: In this study, the anti-parasitic activity of hydroalcoholic extracts of Capparis spinosa Linn (C. spinosa) leaves and fruits with different concentrations (4 to 0.125 mg/ml) was assessed against human isolates of the G. lamblia cysts and incubated at 37℃. After staining Giardia cysts with 0.1% eosin, the lethal percentage and 50% lethal concentration (LC50) of fruit and leave C. spinosa L extracts and metronidazole on G. lamblia cysts were calculated after 3, 6, 24 and 48 hours. Results: Anti-giardia activity of fruit and leaf extracts of C. spinosa was different between concentrations and time points (p<0.005). The lethal effect of both C. spinosa L extracts and metronidazole increased significantly in a concentration - and time–dependent response (P<0.0001). The highest lethal percentage of G. lamblia cysts was observed a concentration of 4 mg / ml of fruit (100%) and leaf (44%) extracts of C. spinosa L after 48 hours, respectively. LC50 values were 0.38 ± 0.02mg/ml for fruit extract, 2.32 ± 0.1 mg/ml for leaf extract and 0.53 ± 0.03 µg/ml for metronidazole after 48hours. Conclusion: C. spinosa can be effective in eliminating Giardia cyst of contaminated environments and water.

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In Vitro Anti-Trypanosoma cruzi Activity of Halophytes from Southern Portugal Reloaded: A Special Focus on Sea Fennel (Crithmum maritimum L.)

Plants ◽

10.3390/plants10112235 ◽

2021 ◽

Vol 10 (11) ◽

pp. 2235

Author(s):

Catarina G. Pereira ◽

Carolina Borsoi Moraes ◽

Caio H. Franco ◽

Clarissa Feltrin ◽

Raphaël Grougnet ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Preparative Thin Layer Chromatography ◽

Selectivity Index ◽

Special Focus ◽

Medicinal Species ◽

Southern Portugal ◽

Parasitic Activity ◽

The One ◽

First Time

Marine halophytes are an outstanding reservoir of natural products and several species have anti-infectious traditional uses. However, reports about their potential use against neglected tropical ailments, such as Chagas disease, are scarce. This work evaluated for the first time the in vitro anti-Trypanosoma cruzi activity of extracts from the aromatic and medicinal species Helichrysum italicum subsp. picardii (Boiss. & Reut.) Franco (Asteraceae, everlasting) and Crithmum maritimum L. (Apiaceae, sea fennel). For that purpose, decoctions, tinctures, and essential oils from everlasting’s flowers and sea fennel’s stems, leaves, and flowers were tested against intracellular amastigotes of two T. cruzi strains. The extract from the sea fennel flower decoction displayed significant anti-trypanosomal activity and no toxicity towards the host cell (EC50 = 17.7 µg/mL, selectivity index > 5.65). Subsequent fractionation of this extract afforded 5 fractions that were re-tested in the same model of anti-parasitic activity. Fraction 1 was the most active and selective (EC50 = 0.47 μg/mL, selectivity index = 59.6) and was submitted to preparative thin-layer chromatography. One major compound was identified, falcarindiol, which was likely the one responsible for the observed anti-trypanosomal activity. This was confirmed using a commercially sourced molecule. Target-fishing studies showed falcarindiol as a ligand of T. cruzi spermidine synthase, pointing to a potential enzyme-inhibiting anti-trypanosomal mechanism of action. Overall, this work shows that sea fennel can provide effective anti-parasitic molecule(s) with potential pharmacological applications in the treatment of CD.

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Maca against Echinococcosis?—A Reverse Approach from Patient to In Vitro Testing

Pathogens ◽

10.3390/pathogens10101335 ◽

2021 ◽

Vol 10 (10) ◽

pp. 1335

Author(s):

Tanja Karpstein ◽

Sheena Chaudhry ◽

Solange Bresson-Hadni ◽

Michael Hayoz ◽

Ghalia Boubaker ◽

...

Keyword(s):

Alveolar Echinococcosis ◽

Parasite Burden ◽

In Vitro Assays ◽

Plastic Stents ◽

In Vitro Proliferation ◽

Cytotoxic Effects ◽

Lepidium Meyenii ◽

Murine Spleen ◽

Parasitic Activity

Drug-based treatment of alveolar echinococcosis (AE) with benzimidazoles is in most cases non-curative, thus has to be taken lifelong. Here, we report on a 56-year-old male AE patient who received standard benzimidazole treatment and biliary plastic stents, and additionally self-medicated himself with the Peruvian plant extract Maca (Lepidium meyenii). After 42 months, viable parasite tissue had disappeared. Based on this striking observation, the anti-echinococcal activity of Maca was investigated in vitro and in mice experimentally infected with Echinococcus multilocularis metacestodes. Albendazole (ABZ)-treated mice and mice treated with an ABZ+Maca combination exhibited a significantly reduced parasite burden compared to untreated or Maca-treated mice. As shown by a newly established UHPLC-MS/MS-based measurement of ABZ-metabolites, the presence of Maca during the treatment did not alter ABZ plasma levels. In vitro assays corroborated these findings, as exposure to Maca had no notable effect on E. multilocularis metacestodes, and in cultures of germinal layer cells, possibly unspecific, cytotoxic effects of Maca were observed. However, in the combined treatments, Maca inhibited the activity of ABZ in vitro. While Maca had no direct anti-parasitic activity, it induced in vitro proliferation of murine spleen cells, suggesting that immunomodulatory properties could have contributed to the curative effect seen in the patient.

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Interaction of Laterispora brevirama and the mycoparasites Sporidesmium sclerotivorum and Teratosperma oligocladum

Canadian Journal of Microbiology ◽

10.1139/m85-148 ◽

1985 ◽

Vol 31 (9) ◽

pp. 786-792 ◽

Cited By ~ 2

Author(s):

W. A. Ayers ◽

P. B. Adams

Keyword(s):

The Other ◽

Aqueous Extracts ◽

Sclerotinia Minor ◽

Secondary Parasite ◽

Parasitic Activity ◽

Parasitic Phase ◽

Do So

Laterispora brevirama, a fungus found in association with the Sclerotinia mycoparasites Sporidesmium sclerotivorum and Teratosperma oligocladum, was markedly similar in morphology to the other two fungi yet differed in its parasitic activity. Laterispora brevirama colonized and proliferated on sclerotia of Sclerotinia minor which had been infected first by Sporidesmium sclerotivorum or T. oligocladum but did not do so in the absence of these specific mycoparasites. Macroconidia of L. brevirama germinated in soil in response to sclerotia infected by Sporidesmium sclerotivorum, and to hyphae of Sporidesmium sclerotivorum. Aqueous extracts of hyphal mats of Sporidesmium sclerotivorum stimulated maximal germination of macroconidia in vitro, although other nutrients also supported germination to a lesser extent. In culture and in its parasitic phase in soil, L. brevirama formed specialized contact cells on the hyphae of Sporidesmium sclerotivorum and T. oligocladum, but never appeared to invade hyphae. Laterispora brevirama added to soil at 1000 macroconidia/g, along with Sporidesmium sclerotivorum at the same concentration, did not influence the rate of infection and destruction of sclerotia of Sclerotinia minor by Sporidesmium sclerotivorum. The resulting numbers of new macroconidia of Sporidesmium sclerotivorum formed in the soil from energy derived from the infected sclerotia, however, were reduced by the presence of L. brevirama. Laterispora brevirama is either a direct parasite of Sporidesmium sclerotivorum and T. oligocladum or is a secondary parasite of Sclerotinia spp. that is active only in association with either of the two primary mycoparasites.

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