The combined effect of iron chelators and classical antimalarials on the in-vitro growth of Plasmodium falciparum

1992 ◽  
Vol 30 (3) ◽  
pp. 273-278 ◽  
Author(s):  
Robyn L. van Zyl ◽  
Ivan Havlik ◽  
Felix S.E. Monteagudo
1996 ◽  
Vol 40 (9) ◽  
pp. 2094-2098 ◽  
Author(s):  
B Pradines ◽  
F Ramiandrasoa ◽  
L K Basco ◽  
L Bricard ◽  
G Kunesch ◽  
...  

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.


2020 ◽  
Vol 119 (6) ◽  
pp. 1879-1887
Author(s):  
Minelly Azevedo da Silva ◽  
Márcia Paranho Veloso ◽  
Kassius de Souza Reis ◽  
Guilherme de Matos Passarini ◽  
Ana Paula de Azevedo dos Santos ◽  
...  

1986 ◽  
Vol 163 (1) ◽  
pp. 179-188 ◽  
Author(s):  
R Schmidt-Ullrich ◽  
J Brown ◽  
H Whittle ◽  
P S Lin

Using the human lymphoblastoid cell line, GM 4672, and PBL of Gambian adults immune to Plasmodium falciparum (Pf) malaria, we have produced human-human hybridomas and selected those that produce mAb against Pf antigens. The fusion frequency, using PWM-stimulated donor lymphocytes was between 6.8 X 10(-5) and 1.5 X 10(-6). Using immune fluorescence, immune precipitation, and Pf in vitro growth inhibition, we cloned four hybridomas that reacted with the Pf Mr 195,000 schizont/merozoite protein. The differences in proteins immune precipitated and in growth inhibition indicate that, during development of protective immunity against Pf malaria, a spectrum of antibodies is produced reacting with different epitopes on the same antigen. Only a portion of these antibodies exhibits biological activity, suggesting that the recognition of certain epitopes is required for the development of a protective immune response.


1987 ◽  
Vol 54 (2) ◽  
pp. 115-122 ◽  
Author(s):  
P. Hermentin ◽  
G. Neunziger ◽  
B. Enders ◽  
W. Dahr

2001 ◽  
Vol 69 (2) ◽  
pp. 1084-1092 ◽  
Author(s):  
Tony Triglia ◽  
Jenny Thompson ◽  
Sonia R. Caruana ◽  
Mauro Delorenzi ◽  
Terry Speed ◽  
...  

ABSTRACT Plasmodium falciparum infections can be fatal, whileP. vivax infections usually are not. A possible factor involved in the greater virulence of P. falciparum is that this parasite grows in red blood cells (RBCs) of all maturities whereasP. vivax is restricted to growth in reticulocytes, which represent only approximately 1% of total RBCs in the periphery. Two proteins, expressed at the apical end of the invasive merozoite stage from P. vivax, have been implicated in the targeting of reticulocytes for invasion by this parasite. A search of the P. falciparum genome databases has identified genes that are homologous to the P. vivax rbp-1 and -2 genes. Two of these genes are virtually identical over a large region of the 5′ end but are highly divergent at the 3′ end. They encode high-molecular-mass proteins of >300 kDa that are expressed in late schizonts and localized to the apical end of the merozoite. To test a potential role in merozoite invasion of RBCs, we analyzed the ability of these proteins to bind to mature RBCs and reticulocytes. No binding to mature RBCs or cell preparations enriched for reticulocytes was detected. We identified a parasite clone that lacks the gene for one of these proteins, showing that the gene is not required for normal in vitro growth. Antibodies to these proteins can inhibit merozoite invasion of RBCs.


2010 ◽  
Vol 9 (1) ◽  
pp. 152 ◽  
Author(s):  
Danny W Wilson ◽  
Brendan S Crabb ◽  
James G Beeson

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