New antitrypanosomal tetranotriterpenoids from &lt;i&gt;Azadirachta Indica&lt;/i&gt;

Githua, Mercy; Hassanali, Ahmed; Keriko, Joseph M.; Murilla, Grace; Ndungu, Mary; Nyagah, Grace

doi:10.4314/ajtcam.v7i3.54776

Cited by 11 publications

(11 citation statements)

References 5 publications

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“…Limonoids are characteristic phytochemicals of the Meliaceae, including Carapa procera ( Table S6 ) [40] , [57] , and numerous limonoids have exhibited antiprotozoal activities [58] – [62] . Six of the eleven C. procera limonoids showed notably strong docking with TbCYP51 (docking energies<−26 kcal/mol).…”

Section: Resultsmentioning

confidence: 99%

In-silico Investigation of Antitrypanosomal Phytochemicals from Nigerian Medicinal Plants

Setzer

Ogungbe

2012

PLoS Negl Trop Dis

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BackgroundHuman African trypanosomiasis (HAT), a parasitic protozoal disease, is caused primarily by two subspecies of Trypanosoma brucei. HAT is a re-emerging disease and currently threatens millions of people in sub-Saharan Africa. Many affected people live in remote areas with limited access to health services and, therefore, rely on traditional herbal medicines for treatment.MethodsA molecular docking study has been carried out on phytochemical agents that have been previously isolated and characterized from Nigerian medicinal plants, either known to be used ethnopharmacologically to treat parasitic infections or known to have in-vitro antitrypanosomal activity. A total of 386 compounds from 19 species of medicinal plants were investigated using in-silico molecular docking with validated Trypanosoma brucei protein targets that were available from the Protein Data Bank (PDB): Adenosine kinase (TbAK), pteridine reductase 1 (TbPTR1), dihydrofolate reductase (TbDHFR), trypanothione reductase (TbTR), cathepsin B (TbCatB), heat shock protein 90 (TbHSP90), sterol 14α-demethylase (TbCYP51), nucleoside hydrolase (TbNH), triose phosphate isomerase (TbTIM), nucleoside 2-deoxyribosyltransferase (TbNDRT), UDP-galactose 4′ epimerase (TbUDPGE), and ornithine decarboxylase (TbODC).ResultsThis study revealed that triterpenoid and steroid ligands were largely selective for sterol 14α-demethylase; anthraquinones, xanthones, and berberine alkaloids docked strongly to pteridine reductase 1 (TbPTR1); chromenes, pyrazole and pyridine alkaloids preferred docking to triose phosphate isomerase (TbTIM); and numerous indole alkaloids showed notable docking energies with UDP-galactose 4′ epimerase (TbUDPGE). Polyphenolic compounds such as flavonoid gallates or flavonoid glycosides tended to be promiscuous docking agents, giving strong docking energies with most proteins.ConclusionsThis in-silico molecular docking study has identified potential biomolecular targets of phytochemical components of antitrypanosomal plants and has determined which phytochemical classes and structural manifolds likely target trypanosomal enzymes. The results could provide the framework for synthetic modification of bioactive phytochemicals, de novo synthesis of structural motifs, and lead to further phytochemical investigations.

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Section: Resultsmentioning

confidence: 99%

In-silico Investigation of Antitrypanosomal Phytochemicals from Nigerian Medicinal Plants

Setzer

Ogungbe

2012

PLoS Negl Trop Dis

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“…Previous studies has shown the in vitro efficacy of the seco -limonoid compound 11 α ,19 β -dihydroxy-7-acetoxy-7-deoxoichangin using the murine macrophage cell line J774·2 as target cell of in vitro infection (Coy Barrera et al 2011), accompanied by an immunomodulatory effect on infected phagocytic cells (murine macrophage and human dendritic cells), which appears to lead to the ‘reactivation’ of the microbicidal capability of infected cells (Granados-Falla et al 2013). In this sense, other studies support the need to confirm the data obtained in in vitro assays by limonoid compounds (as Gedunin, 7-deacetylgedunin and 7-oxo-7-deacetylgedunin) for which over the past years, its potential antiparasitic activity have been assessed against species belonging to the genus Plasmodium, Trypanosoma and Leishmania (Rosas, 2005; Hay et al 2007; Batista et al 2009; Githua et al 2010).…”

Section: Introductionmentioning

confidence: 87%

Seco-limonoid derived from Raputia heptaphylla promotes the control of cutaneous leishmaniasis in hamsters (Mesocricetus auratus)

et al. 2015

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The rational search of novel bioactive molecules against pathogens with immunomodulatory activity is presently one of the most significant approaches to discover and design new therapeutic agents for effective control of infectious diseases, such as the infection caused by Leishmania parasites. In the present study, we evaluated the therapeutic efficacy of the recently characterized immunomodulatory compound 11α,19β-dihydroxy-7-acetoxy-7-deoxoichangin, a seco-limonoid derived from the bark of Raputia heptaphylla (Pittier) using: (1) peritoneal macrophages and (2) Mesocricetus auratus hamsters infected with Leishmania (V.) panamensis and Leishmania (L.) amazonensis. We observed the ability of this seco-limonoid to induce the effective control of the parasite either in vitro [determining an effective concentration 50 (EC50) of 59 µ m at the infection model] and in vivo (inducing clinical improvement or even cure in infected animals treated compared with the groups of animals treated with vehicle solution or meglumine antimoniate).

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“…The extracts were assayed on the three trypanosome strains at concentration ranges of 4000 -1000µg/ml. Each plate was examined with an inverted microscope to determine the minimum inhibitory concentration (MIC) which is the concentration at which no cell with a normal morphology and/or motility was found in comparison to the negative control cultures (Githua et al, 2010).…”

Section: In Vitro Assays For Anti-trypanosomal Activitymentioning

confidence: 99%

In Vitro and in Vivo Anti-Trypanosomal Activities of Methanol Extract of Azadirachta Indica Stem-Bark

Wanzala¹,

Gikonyo²,

Murilla³

et al. 2017

Afr J Tradit Complement Altern Med

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Background: Current chemotherapeutic agents for the treatment of African trypanosomiasis have become largely ineffective, necessitating the search for alternative compounds. The objective of this study was to evaluate in vitro antitrypanosomal activities of methanol extracts of parts of Azadirachta indica against Trypanosoma brucei rhodesiense, Trypanosoma brucei brucei and Trypanosoma evansi and establish the in vivo efficacy of the most active extract. Materials and methods: Maceration of powdered leaves, stem bark and root bark of the plant in methanol afforded three extracts. In vitro assays were carried out with the extracts on the three trypanosome strains in 96-well microtitre plates at concentration ranges of 4000 -1000µg/ml. The most active extract was assayed in vivo using Trypanosoma brucei rhodesiense infected Swiss albino mice at doses of 100, 200 and 400 mg/kg body weight. Melarsoprol and suramin served as positive controls. The infected untreated group served as the negative control. Parasitaemia levels, packed cell volume, body weight changes and mean survival period of all groups were monitored throughout the experimental period. Results: Methanol extract of the stem bark of A.indica was most active in vitro against all the three trypanosome strains (MIC values of 9.93±1.88, 16.25±0.92 and 9.97±0.44µg/ml for T. b. rhodesiense, T. b. brucei and T. evansi, respectively). The extract showed optimum activity at 400 mg/kg and was comparable to the positive control groups. Parasitaemia levels were kept at a significantly low level (p < 0.05) by the extract compared to the negative control. Notably, there was no significant difference (p>0.05) in mean survival time of mice treated with the extract at 400 mg/kg and the positive controls. Conclusion:In vitro and in vivo anti-trypanosomal activities of the methanol extract of A. indica stem bark could be attributed to the presence of constituents of moderate polarity.

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New antitrypanosomal tetranotriterpenoids from <i>Azadirachta Indica</i>

Cited by 11 publications

References 5 publications

In-silico Investigation of Antitrypanosomal Phytochemicals from Nigerian Medicinal Plants

In-silico Investigation of Antitrypanosomal Phytochemicals from Nigerian Medicinal Plants

Seco-limonoid derived from Raputia heptaphylla promotes the control of cutaneous leishmaniasis in hamsters (Mesocricetus auratus)

In Vitro and in Vivo Anti-Trypanosomal Activities of Methanol Extract of Azadirachta Indica Stem-Bark

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