Enantiomeric 1,2,4-Trioxanes Display Equivalent in vitro Antimalarial Activity Versus Plasmodium falciparum Malaria Parasites: Implications for the Molecular Mechanism of Action of the Artemisinins

ChemBioChem ◽  
2005 ◽  
Vol 6 (11) ◽  
pp. 2048-2054 ◽  
Author(s):  
Paul M. O’Neill ◽  
Sarah L. Rawe ◽  
Kristina Borstnik ◽  
Alison Miller ◽  
Stephen A. Ward ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Mechanism ◽  
Falciparum Malaria ◽  
Mechanism Of Action ◽  
Antimalarial Activity ◽  
Plasmodium Falciparum Malaria ◽  
Malaria Parasites ◽  
Molecular Mechanism Of Action

scholarly journals In vitro activities of novel catecholate siderophores against Plasmodium falciparum.

1996 ◽  
Vol 40 (9) ◽  
pp. 2094-2098 ◽  
Author(s):  
B Pradines ◽  
F Ramiandrasoa ◽  
L K Basco ◽  
L Bricard ◽  
G Kunesch ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Mechanism Of Action ◽  
Ribonucleotide Reductase ◽  
Antimalarial Activity ◽  
Iron Chelators ◽  
Resistant Clone ◽  
Iron Deprivation ◽  
Level Of Activity ◽  
Susceptible Clone

The activities of novel iron chelators, alone and in combination with chloroquine, quinine, or artemether, were evaluated in vitro against susceptible and resistant clones of Plasmodium falciparum with a semimicroassay system. N4-nonyl,N1,N8-bis(2,3-dihydroxybenzoyl) spermidine hydrobromide (compound 7) demonstrated the highest level of activity: 170 nM against a chloroquine-susceptible clone and 1 microM against a chloroquine-resistant clone (50% inhibitory concentrations). Compounds 6, 8, and 10 showed antimalarial activity with 50% inhibitory concentrations of about 1 microM. Compound 7 had no effect on the activities of chloroquine, quinine, and artemether against either clone, and compound 8 did not enhance the schizontocidal action of either chloroquine or quinine against the chloroquine-resistant clone. The incubation of compound 7 with FeCI3 suppressed or decreased the in vitro antimalarial activity of compound 7, while no effect was observed with incubation of compound 7 with CuSO4 and ZnSO4. These results suggest that iron deprivation may be the main mechanism of action of compound 7 against the malarial parasites. Chelator compounds 7 and 8 primarily affected trophozoite stages, probably by influencing the activity of ribonucleotide reductase, and thus inhibiting DNA synthesis.

scholarly journals A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria

Nature ◽  
2015 ◽  
Vol 520 (7549) ◽  
pp. 683-687 ◽  
Author(s):  
Alassane Mbengue ◽  
Souvik Bhattacharjee ◽  
Trupti Pandharkar ◽  
Haining Liu ◽  
Guillermina Estiu ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Mechanism ◽  
Falciparum Malaria ◽  
Artemisinin Resistance ◽  
Plasmodium Falciparum Malaria

Efficacy of dihydroartemisinin/piperaquine in patients with non-complicated Plasmodium falciparum malaria in Yaoundé, Cameroon

2021 ◽  
Author(s):  
Mélissa Mairet-Khedim ◽  
Sandrine Nsango ◽  
Christelle Ngou ◽  
Sandie Menard ◽  
Camille Roesch ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Southeast Asia ◽  
Falciparum Malaria ◽  
Gene Polymorphisms ◽  
Plasmodium Falciparum Malaria ◽  
Molecular Profile ◽  
Uncomplicated Plasmodium Falciparum Malaria ◽  
In Vitro Survival ◽  
Phenotypic Susceptibility

Abstract Background Dihydroartemisinin/piperaquine is increasingly used for the treatment of uncomplicated Plasmodium falciparum malaria in Africa. The efficacy of this combination in Cameroon is poorly documented, while resistance to dihydroartemisinin/piperaquine readily spreads in Southeast Asia. Objectives This study evaluated the clinical efficacy of dihydroartemisinin/piperaquine in Cameroon, as well as the molecular profile and phenotypic susceptibility of collected isolates to dihydroartemisinin and piperaquine. Patients and methods Dihydroartemisinin/piperaquine efficacy in 42 days was followed-up for 138 patients presenting non-complicated falciparum malaria. Piperaquine concentration was determined at day 7 for 124 patients. kelch13 gene polymorphisms (n = 150) and plasmepsin2 gene amplification (n = 148) were determined as molecular markers of resistance to dihydroartemisinin and piperaquine, respectively. Parasite susceptibility to dihydroartemisinin and piperaquine was determined using validated in vitro survival assays. Results The efficacy of dihydroartemisinin/piperaquine treatment was 100% after PCR correction. The reinfections were not associated with a variation of piperaquine concentration at day 7. Ninety-six percent (144/150) of the samples presented a WT allele of the kelch13 gene. Two percent (3/150) presented the non-synonymous mutation A578S, which is not associated with resistance to dihydroartemisinin. No duplication of the plasmepsin2 gene was observed (0/148). All the samples tested in vitro by survival assays (n = 87) were susceptible to dihydroartemisinin and piperaquine. Conclusions Dihydroartemisinin/piperaquine has demonstrated excellent therapeutic efficacy with no evidence of emerging artemisinin or piperaquine resistance in Yaoundé, Cameroon. This observation suggests that dihydroartemisinin/piperaquine could be a sustainable therapeutic solution for P. falciparum malaria if implemented in areas previously free of artemisinin- and piperaquine-resistant parasites, unlike Southeast Asia.

Erratum to “Molecular mechanism of action of oxazolinoanthracyclines in cells derived from human solid tumors. Part 2” [Toxicol. in Vitro 46 (2018) 323–334]

2018 ◽  
Vol 48 ◽  
pp. 350-352
Author(s):  
Marta Denel-Bobrowska ◽  
Małgorzata Łukawska ◽  
Barbara Bukowska ◽  
Arkadiusz Gajek ◽  
Irena Oszczapowicz ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Molecular Mechanism ◽  
Mechanism Of Action ◽  
Human Solid Tumors ◽  
Molecular Mechanism Of Action ◽  
In Cells
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