scholarly journals A Study of Synergy of Combination of Eosin B with Chloroquine, Artemisinin, and Sulphadoxine-Pyrimethamine on Plasmodium falciparum In Vitro and Plasmodium berghei In Vivo

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Sedigheh Sadeghi ◽  
Zarrintaj Valadkhani ◽  
Alireza Sadeghi Tafreshi ◽  
Mohammad Arjmand ◽  
Hossein Nahravanian ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Berghei ◽  
Combination Index ◽  
Antimalarial Drugs ◽  
Live Cells ◽  
Eosin B ◽  
Suppression Test ◽  
Sulphadoxine Pyrimethamine

Background and Objectives. Artemisinin is the popular antimalarial medication, but it has to be used in combination with other drugs as its monotherapy causes resistance. The effectiveness of eosin B, a laboratory stain, as a competent antimalarial agent was identified earlier. It was tested in combination with different antimalarial drugs such as artesunate (a derivative of artemisinin) or chloroquine or sulphadoxine-pyrimethamine in vitro on Plasmodium falciparum and in vivo on Plasmodium berghei using Peter’s suppression test. Methods. Drug assessment was carried out singly or in combination on Plasmodium falciparum in vitro using the candle jar method at three inhibitory concentrations. Percent parasitemia of live cells was obtained by microscopic counting. Peter’s suppression test was carried out on mice infected with Plasmodium berghei after 3 administration of the drugs singly and in combination, and parasites were counted by microscopy for 10 days. Results. Synergy was exhibited by isobolograms of eosin B combined with artesunate and sulphadoxine-pyrimethamine with more than 10 fold reduction of all drugs in vitro. A good combination index was obtained with artesunate at 50% inibitory concentration with 3.4 nM eosin B and 1.7 nM artesunate in contrast to 124 nM eosin B and 7.6 nM artesunate singly. In vivo studies also showed a considerable lowering of the effective dose of eosin B 30 mg/kg: artesunate 3 mg/kg with 200 mg/kg eosin B and 60 mg/kg artesunate separately. Sulphadoxine-pyrimethamine seemed to have the greatest synergistic effect with a combination index of 0.007, but this could be due to it consisting of a combination of three drugs. Eosin B’s combination index with chloroquine was fair, and in vivo tests too did not show as much competence as the other two drugs. Conclusion and Interpretation. It can be concluded that eosin B can be used in combination with antimalarial drugs with favorable results.

Plants as Sources of Antimalarial Drugs, Part 4: Activity of Brucea javanica Fruits Against Chloroquine-Resistant Plasmodium falciparum in vitro and Against Plasmodium berghei in vivo

1987 ◽  
Vol 50 (1) ◽  
pp. 41-48 ◽  
Author(s):  
Melanie J. O'Neill ◽  
Dorothy H. Bray ◽  
Peter Boardman ◽  
Kit L. Chan ◽  
J. David Phillipson ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Berghei ◽  
Antimalarial Drugs ◽  
Brucea Javanica

The in vitro antimalarial interaction of 9-hydroxycalabaxanthone and α-mangostin with mefloquine/artesunate

2014 ◽  
Vol 60 (1) ◽  
Author(s):  
Wanna Chaijaroenkul ◽  
Kesara Na-Bangchang
Keyword(s):  
Plasmodium Falciparum ◽  
Multidrug Resistance ◽  
Drug Concentration ◽  
Combination Index ◽  
Antimalarial Drugs ◽  
Antagonistic Effect ◽  
Parasite Growth ◽  
Major Health Problem ◽  
Major Health

AbstractMultidrug resistance Plasmodium falciparum is the major health problem in Thailand. Discovery and development of new antimalarial drugs with novel modes of action is urgently required. The aim of the present study was to investigate the antimalarial interaction of 9-hydroxycalabaxanthone and α-mangostin with the standard antimalarial drugs mefloquine and artesunate in chloroquine sensitive (3D7) and chloroquine resistant (K1) P. falciparum clones in vitro. Median (range) IC50 (drug concentration which produces 50% parasite growth inhibition) values of the 9-hydroxycalabaxanthone, α-mangostin, artesunate and mefloquine for 3D7 vs K1 clones were 1.5 (0.9-2.1) vs 1.2 (1.1-1.6) μM, 17.9 (15.7.0-20.0) vs 9.7 (6.0-14.0) μM, 1.0 (0.4-3.0) vs 1.7 (1.0-2.5) nM, and 13.3 (11.1-13.3) vs 7.1 (6.7-12.2) nM, respectively. Analysis of isobologram and combination index (CI) of 9-hydroxycalabaxanthone with artesunate or mefloquine showed synergistic and indifference antimalarial interaction, respectively. α-mangostin-artesunate combination exhibited a slight antagonistic effect of antimalarial interaction, whereas α-mangostin and mefloquine combination showed indifference interaction in both clones. The combination of 9-hydroxycalabaxanthone with α-mangostin showed the synergistic antimalarial interaction in both clones

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

ChemInform ◽  
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

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

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4095 ◽  
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.

Resistance of Plasmodium falciparum to antimalarial drugs in a highly endemic area of southern Viet Nam: a study in vivo and in vitro

2001 ◽  
Vol 95 (3) ◽  
pp. 325-329 ◽  
Author(s):  
Nguyen Mai Huong ◽  
Sean Hewitt ◽  
Timothy M.E. Davis ◽  
Le Duc Dao ◽  
Tran Quoc Toan ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Endemic Area ◽  
Antimalarial Drugs ◽  
Viet Nam

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

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
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.

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

2015 ◽  
Vol 25 (11) ◽  
pp. 2308-2313 ◽  
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

scholarly journals Complex Polymorphisms in the Plasmodium falciparum Multidrug Resistance Protein 2 Gene and Its Contribution to Antimalarial Response

2014 ◽  
Vol 58 (12) ◽  
pp. 7390-7397 ◽  
Author(s):  
Maria Isabel Veiga ◽  
Nuno S. Osório ◽  
Pedro Eduardo Ferreira ◽  
Oscar Franzén ◽  
Sabina Dahlstrom ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Multidrug Resistance ◽  
Abc Transporter ◽  
Parasite Clearance ◽  
Antimalarial Drugs ◽  
Multidrug Resistance Protein ◽  
Content Type ◽  
Resistance Protein

ABSTRACTPlasmodium falciparumhas the capacity to escape the actions of essentially all antimalarial drugs. ATP-binding cassette (ABC) transporter proteins are known to cause multidrug resistance in a large range of organisms, including theApicomplexaparasites.P. falciparumgenome analysis has revealed two genes coding for the multidrug resistance protein (MRP) type of ABC transporters:Pfmrp1, previously associated with decreased parasite drug susceptibility, and the poorly studiedPfmrp2. The role ofPfmrp2polymorphisms in modulating sensitivity to antimalarial drugs has not been established. We herein report a comprehensive account of thePfmrp2genetic variability in 46 isolates from Thailand. A notably high frequency of 2.8 single nucleotide polymorphisms (SNPs)/kb was identified for this gene, including some novel SNPs. Additionally, we found thatPfmrp2harbors a significant number of microindels, some previously not reported. We also investigated the potential association of the identifiedPfmrp2polymorphisms with alteredin vitrosusceptibility to several antimalarials used in artemisinin-based combination therapy and with parasite clearance time. Association analysis suggestedPfmrp2polymorphisms modulate the parasite'sin vitroresponse to quinoline antimalarials, including chloroquine, piperaquine, and mefloquine, and association within vivoparasite clearance. In conclusion, our study reveals that thePfmrp2gene is the most diverse ABC transporter known inP. falciparumwith a potential role in antimalarial drug resistance.

scholarly journals Chemical Attenuation of Plasmodium berghei Sporozoites Induces Sterile Immunity in Mice

2008 ◽  
Vol 76 (3) ◽  
pp. 1193-1199 ◽  
Author(s):  
Lisa A. Purcell ◽  
Stephanie K. Yanow ◽  
Moses Lee ◽  
Terry W. Spithill ◽  
Ana Rodriguez
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Berghei ◽  
Alkylating Agent ◽  
Blood Stage ◽  
Wild Type ◽  
Vaccine Strategy ◽  
Liver Stage ◽  
Stage Development

ABSTRACT Radiation and genetic attenuation of Plasmodium sporozoites are two approaches for whole-organism vaccines that protect against malaria. We evaluated chemical attenuation of sporozoites as an alternative vaccine strategy. Sporozoites were treated with the DNA sequence-specific alkylating agent centanamycin, a compound that significantly affects blood stage parasitemia and transmission of murine malaria and also inhibits Plasmodium falciparum growth in vitro. Here we show that treatment of Plasmodium berghei sporozoites with centanamycin impaired parasite function both in vitro and in vivo. The infection of hepatocytes by sporozoites in vitro was significantly reduced, and treated parasites showed arrested liver stage development. Inoculation of mice with sporozoites that were treated in vitro with centanamycin failed to produce blood stage infections. Furthermore, BALB/c and C57BL/6 mice vaccinated with treated sporozoites were protected against subsequent challenge with wild-type sporozoites. Our findings demonstrate that chemically attenuated sporozoites could be a viable alternative for the production of an effective liver stage vaccine for malaria.

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