Homology modeling and docking studies of &lt;i&gt;Plasmodium falciparum&lt;/i&gt; telomerase reverse transcriptase with berberine and some of its derivatives

Parida, Pratap; Kalita, S. N.; Yadav, Rajkumar; Shankar, Brajesh

doi:10.3329/bjp.v9i1.17535

Cited by 4 publications

(4 citation statements)

References 23 publications

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“…2002; Parida et al. 2014) while fagaronine is demonstrated to inhibit plasmodial DNA topoisomerases I and II. Fagaronine also acts as a DNA intercalating agent (Larsen et al.…”

Section: Discussionmentioning

confidence: 99%

Methanol extracts of Fagara zanthoxyloides leaves possess antimalarial effects and normalizes haematological and biochemical status of Plasmodium berghei-passaged mice

Enechi

Amah

Okagu

et al. 2019

Pharmaceutical Biology

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Context: The resistance of Plasmodium species to many available antimalarials calls for a continuous search for newer antimalarial agents. One possible source of new antimalarials is from natural sources such as Fagara zanthoxyloides Lam (Rutaceae), a medicinal plant used traditionally for treating malaria in South-Eastern Nigeria, Uganda and Asia.Objectives: To investigate the application of methanol extracts of F. zanthoxyloides in combating malaria infection and its associated disorders.Materials and methods: Methanol extracts of F. zanthoxyloides leaves (MEFZ) were evaluated for in vivo antimalarial activity. MEFZ at doses of 200, 400, and 600 mg/kg/d were administered orally for 4 consecutive days (days 0–4) to P. berghei-infected mice. The possible ameliorative effects of MEFZ on malaria-associated organ malfunctions were also assessed.Results: At 200, 400 and 600 mg/kg b.w., respectively, MEFZ produced 82.37% and 68.39%, 84.84%, and 90.75%, 95.95% and 92.67% chemosuppression and inhibition of P. berghei, respectively, comparable to 98.67% and 97.29% by combisunate, a standard antimalarial. The IC50 of MEFZ was estimated to be 235.23 mg/kg b.w. Similarly, treatment of parasitized mice with MEFZ significantly restored the malaria-modified haematological and biochemical status of the parasitized-MEFZ-treated mice compared with parasitized-untreated mice. MEFZ was tolerable up to 5000 mg/kg b.w dose; hence, the LD50 is above 5000 mg/kg b.w.Discussion and conclusions: The results of this curative assay demonstrated that MEFZ has antimalarial effects and normalized haematological and biochemical aberrations generated by malaria. The isolation of the antimalarial principles in MEFZ is warranted; they could be lead molecules for the development of new antimalarials.

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“…2002; Parida et al. 2014) while fagaronine is demonstrated to inhibit plasmodial DNA topoisomerases I and II. Fagaronine also acts as a DNA intercalating agent (Larsen et al.…”

Section: Discussionmentioning

confidence: 99%

Methanol extracts of Fagara zanthoxyloides leaves possess antimalarial effects and normalizes haematological and biochemical status of Plasmodium berghei-passaged mice

Enechi

Amah

Okagu

et al. 2019

Pharmaceutical Biology

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“…The authors cultured P. falciparum 3D7 strain parasites in culture medium with 10 times the IC 50 value of berberine chloride for 3 months in an attempt to produce a berberine-resistant malaria parasite, but the authors were unable to obtain such a parasite. A previous study reported that berberine inhibits the telomerase activity of P. falciparum K1 strain [ 18 , 19 ]. Telomeres play important roles in eukaryotic cells in maintaining genome stability and ensuring accurate DNA replication.…”

Section: Discussionmentioning

confidence: 99%

Screening of a library of traditional Chinese medicines to identify anti-malarial compounds and extracts

Nonaka

Murata

Takano

et al. 2018

Malar J

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BackgroundMalaria is a major infectious disease in the world. In 2015, approximately 212 million people were infected and 429,000 people were killed by this disease. Plasmodium falciparum, which causes falciparum malaria, is becoming resistant to artemisinin (ART) in Southeast Asia; therefore, new anti-malarial drugs are urgently needed. Some excellent anti-malarial drugs, such as quinine or ART, were originally obtained from natural plants. Hence, the authors screened a natural product library comprising traditional Chinese medicines (TCMs) to identify compounds/extracts with anti-malarial effects.MethodsThe authors performed three assays: a malaria growth inhibition assay (GIA), a cytotoxicity assay, and a malaria stage-specific GIA. The malaria GIA revealed the anti-malarial ability and half-maximal inhibitory concentrations (IC50) of the natural products, whereas the malaria stage-specific GIA revealed the point in the malaria life cycle where the products exerted their anti-malarial effects. The toxicity of the products to the host cells was evaluated with the cytotoxicity assay.ResultsFour natural compounds (berberine chloride, coptisine chloride, palmatine chloride, and dehydrocorydaline nitrate) showed strong anti-malarial effects (IC50 < 50 nM), and low cytotoxicity (cell viability > 90%) using P. falciparum 3D7 strain. Two natural extracts (Phellodendri cortex and Coptidis rhizoma) also showed strong antiplasmodial effects (IC50 < 1 µg/ml), and low cytotoxicity (cell viability > 80%). These natural products also demonstrated anti-malarial capability during the trophozoite and schizont stages of the malaria life cycle.ConclusionsThe authors identified four compounds (berberine chloride, coptisine chloride, palmatine chloride, and dehydrocorydaline nitrate) and two extracts (Phellodendri cortex and Coptidis rhizoma) with anti-malarial activity, neither of which had previously been described. The IC50 values of the compounds were comparable to that of chloroquine and better than that of pyrimethamine. These compounds and extracts derived from TCMs thus show promise as potential future anti-malarial drugs.

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“…The likely mechanism of action of the alkaloids is explained by their ability to form complexes with the heme group and inhibit the formation of b-hematin ( O'Neill et al, 2009 ; Kelly et al, 2009 ; Bouquet et al, 2012 ). The fagaronin inhibits topoisomerases I and II and acts as a DNA-intercalating agent ( Larsen et al, 1993 ), and berberine inhibits the Plasmodium telomerase ( Sriwilaijareon et al, 2002 ; Parida et al, 2014 ). The alkaloid flavopereirin also was active against L. amazonensis promastigotes, and this activity is attributable to oligopeptidase binding ( Silva e Silva et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Activity of the genus Zanthoxylum against diseases caused by protozoa: A systematic review

et al. 2023

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Neglected diseases (NDs) are treated with a less varied range of drugs, with high cost and toxicity, which makes the search for therapeutic alternatives important. In this context, plants, such as those from the genus Zanthoxylum, can be promising due to active substances in their composition. This study evaluates the potential of species from this genus to treat NDs. Initially, a protocol was developed to carry out a systematic review approved by Prospero (CRD42020200438). The databases PubMed, BVS, Scopus, Science Direct, and Web of Science were used with the following keywords: “zanthoxylum,” “xanthoxylums,” “fagaras,” “leishmaniasis,” “chagas disease,” “malaria,” and “African trypanosomiasis.” Two independent evaluators analyzed the title and abstract of 166 articles, and 122 were excluded due to duplicity or for not meeting the inclusion criteria. From the 44 selected articles, results of in vitro/in vivo tests were extracted. In vitro studies showed that Z. rhoifolium, through the alkaloid nitidine, was active against Plasmodium (IC50 <1 μg/ml) and Leishmania (IC50 <8 μg/ml), and selective for both (>10 and >30, respectively). For Chagas disease, the promising species (IC50 <2 μg/ml) were Z. naranjillo and Z. minutiflorum, and for sleeping sickness, the species Z. zanthoxyloides (IC50 <4 μg/ml) stood out. In the in vivo analysis, the most promising species were Z. rhoifolium and Z. chiloperone. In summary, the species Z. rhoifolium, Z. naranjillo, Z. minutiflorum, Z. zanthoxyloides, and Z. chiloperone are promising sources of active molecules for the treatment of NDs.

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Homology modeling and docking studies of <i>Plasmodium falciparum</i> telomerase reverse transcriptase with berberine and some of its derivatives

Cited by 4 publications

References 23 publications

Methanol extracts of Fagara zanthoxyloides leaves possess antimalarial effects and normalizes haematological and biochemical status of Plasmodium berghei-passaged mice

Methanol extracts of Fagara zanthoxyloides leaves possess antimalarial effects and normalizes haematological and biochemical status of Plasmodium berghei-passaged mice

Screening of a library of traditional Chinese medicines to identify anti-malarial compounds and extracts

Activity of the genus Zanthoxylum against diseases caused by protozoa: A systematic review

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