In vitro and in vivo antimalarial activity of the volatile oil of Cyperus articulatus (Cyperaceae)

ABSTRACT Malaria is a disease of global tropical distribution, being endemic in more than 90 countries and responsible for about 212 million cases worldwide in 2016. To date, the strategies used to eradicate this disease have been ineffective, without specific preventive measures such as vaccines. Currently, the existing therapeutic arsenal is limited and has become ineffective against the expansion of artemisinin-resistant Plasmodium, demonstrating the need for studies that would allow the development of new compounds against this disease. In this context, we studied the volatile oil obtained from rhizomes of Cyperus articulatus (VOCA), a plant species commonly found in the Amazon region and popularly used as a therapeutic alternative for the treatment of malaria, in order to confirm its potential as an antimalarial agent by in vitro and in vivo assays. We cultured Plasmodium falciparum W2 (chloroquine-resistant) and 3D7 (chloroquine-sensitive) strains in erythrocytes and exposed them to VOCA at different concentrations in 96-well microplates. In vivo antimalarial activity was tested in BALB/c mice inoculated with approximately 106 erythrocytes infected with Plasmodium berghei. VOCA showed a high antimalarial potential against the two P. falciparum strains, with IC50 = 1.21 μg mL-1 for W2 and 2.30 μg mL-1 for 3D7. VOCA also significantly reduced the parasitemia and anemia induced by P. berghei in mice. Our results confirmed the antimalarial potential of the volatile oil of Cyperus articulatus.

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Antimalarial Activity of Phenazines from Lapachol, β-Lapachone and Its Derivatives Against Plasmodium falciparum in vitro and Plasmodium berghei in vivo.

ChemInform ◽

10.1002/chin.200426191 ◽

2004 ◽

Vol 35 (26) ◽

Author(s):

Valter F. de Andrade-Neto ◽

Marilia O. F. Goulart ◽

Jorge F. da Silva Filho ◽

Matuzalem J. da Silva ◽

Maria do Carmo F. R. Pinto ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Plasmodium Berghei ◽

Antimalarial Activity

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The Development of Novel Compounds Against Malaria: Quinolines, Triazolpyridines, Pyrazolopyridines and Pyrazolopyrimidines

Molecules ◽

10.3390/molecules24224095 ◽

2019 ◽

Vol 24 (22) ◽

pp. 4095 ◽

Cited By ~ 11

Author(s):

Luiz C. S. Pinheiro ◽

Lívia M. Feitosa ◽

Marilia O. Gandi ◽

Flávia F. Silveira ◽

Nubia Boechat

Keyword(s):

Plasmodium Falciparum ◽

Mouse Model ◽

Infected Mouse ◽

Plasmodium Berghei ◽

Medicinal Chemistry ◽

Quinoline Derivatives ◽

Dihydroorotate Dehydrogenase ◽

New Compounds

Based on medicinal chemistry tools, new compounds for malaria treatment were designed. The scaffolds of the drugs used to treat malaria, such as chloroquine, primaquine, amodiaquine, mefloquine and sulfadoxine, were used as inspiration. We demonstrated the importance of quinoline and non-quinoline derivatives in vitro with activity against the W2 chloroquine-resistant (CQR) Plasmodium falciparum clone strain and in vivo against Plasmodium berghei-infected mouse model. Among the quinoline derivatives, new hybrids between chloroquine and sulfadoxine were designed, which gave rise to an important prototype that was more active than both chloroquine and sulfadoxine. Hybrids between chloroquine–atorvastatin and primaquine–atorvastatin were also synthesized and shown to be more potent than the parent drugs alone. Additionally, among the quinoline derivatives, new mefloquine derivatives were synthesized. Among the non-quinoline derivatives, we obtained excellent results with the triazolopyrimidine nucleus, which gave us prototype I that inspired the synthesis of new heterocycles. The pyrazolopyrimidine derivatives stood out as non-quinoline derivatives that are potent inhibitors of the P. falciparum dihydroorotate dehydrogenase (PfDHODH) enzyme. We also examined the pyrazolopyridine and pyrazolopyrimidine nuclei.

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Andrographolide: A Novel Antimalarial Diterpene Lactone Compound fromAndrographis paniculataand Its Interaction with Curcumin and Artesunate

Journal of Tropical Medicine ◽

10.1155/2011/579518 ◽

2011 ◽

Vol 2011 ◽

pp. 1-6 ◽

Cited By ~ 27

Author(s):

Kirti Mishra ◽

Aditya P. Dash ◽

Nrisingha Dey

Keyword(s):

Plasmodium Falciparum ◽

Life Span ◽

Plasmodium Berghei ◽

Antimalarial Activity ◽

Andrographis Paniculata ◽

Antiplasmodial Activity ◽

Template Molecule

Andrographolide (AND), the diterpene lactone compound, was purified by HPLC from the methanolic fraction of the plantAndrographis paniculata. The compound was found to have potent antiplasmodial activity when tested in isolation and in combination with curcumin and artesunate against the erythrocytic stages ofPlasmodium falciparum in vitroandPlasmodium bergheiANKAin vivo. IC50s for artesunate (AS), andrographolide (AND), and curcumin (CUR) were found to be 0.05, 9.1 and 17.4 μM, respectively. The compound (AND) was found synergistic with curcumin (CUR) and addictively interactive with artesunate (AS).In vivo, andrographolide-curcumin exhibited better antimalarial activity, not only by reducing parasitemia (29%), compared to the control (81%), but also by extending the life span by 2-3 folds. Being nontoxic to thein vivosystem this agent can be used as template molecule for designing new derivatives with improved antimalarial properties.

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New quinoline derivatives demonstrate a promising antimalarial activity against Plasmodium falciparum in vitro and Plasmodium berghei in vivo

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2015.04.014 ◽

2015 ◽

Vol 25 (11) ◽

pp. 2308-2313 ◽

Cited By ~ 24

Author(s):

Roberta Reis Soares ◽

José Marcio Fernandes da Silva ◽

Bianca Cecheto Carlos ◽

Camila Campos da Fonseca ◽

Laila Salomé Araújo de Souza ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Plasmodium Berghei ◽

Antimalarial Activity ◽

Quinoline Derivatives

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Antimalarial activity of phenazines from lapachol, β-lapachone and its derivatives against Plasmodium falciparum in vitro and Plasmodium berghei in vivo

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2003.12.069 ◽

2004 ◽

Vol 14 (5) ◽

pp. 1145-1149 ◽

Cited By ~ 205

Author(s):

Valter F de Andrade-Neto ◽

Marı́lia O.F Goulart ◽

Jorge F da Silva Filho ◽

Matuzalém J da Silva ◽

Maria do Carmo F.R Pinto ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Plasmodium Berghei ◽

Antimalarial Activity

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Effect of Solanun nudum Extracts on the Liver of Mice Infected with Plasmodium berghei

The American Journal of Chinese Medicine ◽

10.1142/s0192415x01000496 ◽

2001 ◽

Vol 29 (03n04) ◽

pp. 477-484 ◽

Cited By ~ 9

Author(s):

Echeverri Marcela ◽

Blair Silvia ◽

Carmona Jaime ◽

Pérez Pilar

Keyword(s):

Plasmodium Falciparum ◽

Therapeutic Effect ◽

Aqueous Extract ◽

Plasmodium Berghei ◽

Antimalarial Activity ◽

In Vivo Studies ◽

Hexane Extracts ◽

Liver Changes

The plant Solanum nudum has been used by the community of Tumaco (Nariño, Colombia) as a cure for malaria. Our group has confirmed the in vitro antimalarial activity against the strain of Plasmodium falciparum FCB-2. During our in vivo studies on the therapeutic effect of Solanum nudum extracts on mice infected with Plasmodium berghei, we observed yellowish tint in the palms of mice treated with the aqueous extract via ip at a concentration of 2.4% w/vol. This findings suggested the need to carry out a histology study of the liver. Plasmodium berghei infection produces liver changes such as the deposit of pigment inn sinusoids, leucocytes infiltration, esteatosis and necrosis of hepatocytes. These changes were also observed when the mice were treated with methane and hexane extracts from Solanum nudum; however necrosis of hepatocytes in mice infected with malaria decreased 47–65% when they were administered wither with queous extract, or tumacoside A and degraded diosgenone, compounds from methane and hexane extracts of Solanum nudum respectively.

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Stage-dependent effect of deferoxamine on growth of Plasmodium falciparum in vitro

Blood ◽

10.1182/blood.v76.6.1250.1250 ◽

1990 ◽

Vol 76 (6) ◽

pp. 1250-1255 ◽

Cited By ~ 36

Author(s):

S Whitehead ◽

TE Peto

Keyword(s):

Plasmodium Falciparum ◽

Growth Inhibition ◽

Antimalarial Activity ◽

Clinical Malaria ◽

Inhibitory Effect ◽

Parasite Development ◽

And Control ◽

Speed Of Onset

Abstract Deferoxamine (DF) has antimalarial activity that can be demonstrated in vitro and in vivo. This study is designed to examine the speed of onset and stage dependency of growth inhibition by DF and to determine whether its antimalarial activity is cytostatic or cytocidal. Growth inhibition was assessed by suppression of hypoxanthine incorporation and differences in morphologic appearance between treated and control parasites. Using synchronized in vitro cultures of Plasmodium falciparum, growth inhibition by DF was detected within a single parasite cycle. Ring and nonpigmented trophozoite stages were sensitive to the inhibitory effect of DF but cytostatic antimalarial activity was suggested by evidence of parasite recovery in later cycles. However, profound growth inhibition, with no evidence of subsequent recovery, occurred when pigmented trophozoites and early schizonts were exposed to DF. At this stage in parasite development, the activity of DF was cytocidal and furthermore, the critical period of exposure may be as short as 6 hours. These observations suggest that iron chelators may have a role in the treatment of clinical malaria.

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Antimalarial Effect of the Total Glycosides of the Medicinal Plant, Ranunculus japonicus

Pathogens ◽

10.3390/pathogens10050532 ◽

2021 ◽

Vol 10 (5) ◽

pp. 532

Author(s):

Hae-Soo Yun ◽

Sylvatrie-Danne Dinzouna-Boutamba ◽

Sanghyun Lee ◽

Zin Moon ◽

Dongmi Kwak ◽

...

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Plasmodium Berghei ◽

Antimalarial Activity ◽

Hematological Parameters ◽

Significant Inhibition ◽

Ic50 Values ◽

The Republic

In traditional Chinese medicine, Ranunculus japonicus has been used to treat various diseases, including malaria, and the young stem of R. japonicus is consumed as a food in the Republic of Korea. However, experimental evidence of the antimalarial effect of R. japonicus has not been evaluated. Therefore, the antimalarial activity of the extract of the young stem of R. japonicus was evaluated in vitro using both chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) strains; in vivo activity was evaluated in Plasmodium berghei-infected mice via oral administration followed by a four-day suppressive test focused on biochemical and hematological parameters. Exposure to extracts of R. japonicus resulted in significant inhibition of both chloroquine-sensitive (3D7) and resistant (Dd2) strains of P. falciparum, with IC50 values of 6.29 ± 2.78 and 5.36 ± 4.93 μg/mL, respectively. Administration of R. japonicus also resulted in potent antimalarial activity against P. berghei in infected mice with no associated toxicity; treatment also resulted in improved hepatic, renal, and hematologic parameters. These results demonstrate the antimalarial effects of R. japonicus both in vitro and in vivo with no apparent toxicity.

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Antimalarial activity of betulinic acid and derivatives in vitro against Plasmodium falciparum and in vivo in P. berghei-infected mice

Parasitology Research ◽

10.1007/s00436-009-1394-0 ◽

2009 ◽

Vol 105 (1) ◽

pp. 275-279 ◽

Cited By ~ 46

Author(s):

Matheus Santos de Sá ◽

José Fernando Oliveira Costa ◽

Antoniana Ursine Krettli ◽

Mariano Gustavo Zalis ◽

Gabriela Lemos de Azevedo Maia ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Betulinic Acid ◽

Antimalarial Activity

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Computational Chemogenomics Drug Repositioning Strategy Enables the Discovery of Epirubicin as a New Repurposed Hit for Plasmodium falciparum and P. vivax

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02041-19 ◽

2020 ◽

Vol 64 (9) ◽

Author(s):

Letícia Tiburcio Ferreira ◽

Juliana Rodrigues ◽

Gustavo Capatti Cassiano ◽

Tatyana Almeida Tavella ◽

Kaira Cristina Peralis Tomaz ◽

...

Keyword(s):

Plasmodium Falciparum ◽

In Silico ◽

Antimalarial Activity ◽

Drug Repositioning ◽

Dna Gyrase ◽

Plasmodium Yoelii ◽

Computer Assisted ◽

Content Type

ABSTRACT Widespread resistance against antimalarial drugs thwarts current efforts for controlling the disease and urges the discovery of new effective treatments. Drug repositioning is increasingly becoming an attractive strategy since it can reduce costs, risks, and time-to-market. Herein, we have used this strategy to identify novel antimalarial hits. We used a comparative in silico chemogenomics approach to select Plasmodium falciparum and Plasmodium vivax proteins as potential drug targets and analyzed them using a computer-assisted drug repositioning pipeline to identify approved drugs with potential antimalarial activity. Among the seven drugs identified as promising antimalarial candidates, the anthracycline epirubicin was selected for further experimental validation. Epirubicin was shown to be potent in vitro against sensitive and multidrug-resistant P. falciparum strains and P. vivax field isolates in the nanomolar range, as well as being effective against an in vivo murine model of Plasmodium yoelii. Transmission-blocking activity was observed for epirubicin in vitro and in vivo. Finally, using yeast-based haploinsufficiency chemical genomic profiling, we aimed to get insights into the mechanism of action of epirubicin. Beyond the target predicted in silico (a DNA gyrase in the apicoplast), functional assays suggested a GlcNac-1-P-transferase (GPT) enzyme as a potential target. Docking calculations predicted the binding mode of epirubicin with DNA gyrase and GPT proteins. Epirubicin is originally an antitumoral agent and presents associated toxicity. However, its antiplasmodial activity against not only P. falciparum but also P. vivax in different stages of the parasite life cycle supports the use of this drug as a scaffold for hit-to-lead optimization in malaria drug discovery.

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