scholarly journals Intrinsic fluorescence properties of antimalarial pyrido[1,2-a]benzimidazoles facilitate subcellular accumulation and mechanistic studies in the human malaria parasite Plasmodium falciparum

2020 ◽  
Vol 18 (42) ◽  
pp. 8668-8676
Author(s):  
Constance M. Korkor ◽  
Larnelle F. Garnie ◽  
Leah Amod ◽  
Timothy J. Egan ◽  
Kelly Chibale
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Parasite ◽  
Intrinsic Fluorescence ◽  
Fluorescence Properties ◽  
Benzimidazole Derivatives ◽  
Inhibition Assay ◽  
Mechanistic Studies ◽  
Human Malaria Parasite ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum

Intrinsic fluorescence properties, docking and a hemozoin inhibition assay were employed to study the mechanism of action of two structurally related pyrido-[1,2-a]benzimidazole derivatives.

Commitment to sexual differentiation in the human malaria parasite, Plasmodium falciparum

Parasitology ◽  
2000 ◽  
Vol 121 (2) ◽  
pp. 127-133 ◽  
Author(s):  
T. G. SMITH ◽  
P. LOURENÇO ◽  
R. CARTER ◽  
D. WALLIKER ◽  
L. C. RANFORD-CARTWRIGHT
Keyword(s):  
Plasmodium Falciparum ◽  
Sexual Differentiation ◽  
Malaria Parasite ◽  
Human Malaria Parasite ◽  
Human Malaria ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum

scholarly journals PfPDE1, a novel cGMP-specific phosphodiesterase from the human malaria parasite Plasmodium falciparum

2005 ◽  
Vol 392 (1) ◽  
pp. 221-229 ◽  
Author(s):  
Keizo Yuasa ◽  
Fumika Mi-Ichi ◽  
Tamaki Kobayashi ◽  
Masaya Yamanouchi ◽  
Jun Kotera ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Cyclic Nucleotide ◽  
Malaria Parasite ◽  
Catalytic Domain ◽  
Hydrolytic Activity ◽  
Human Malaria Parasite ◽  
Pde Inhibitors ◽  
Ic50 Value ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum

This is the first report of molecular characterization of a novel cyclic nucleotide PDE (phosphodiesterase), isolated from the human malaria parasite Plasmodium falciparum and designated PfPDE1. PfPDE1 cDNA encodes an 884-amino-acid protein, including six putative transmembrane domains in the N-terminus followed by a catalytic domain. The PfPDE1 gene is a single-copy gene consisting of two exons and a 170 bp intron. PfPDE1 transcripts were abundant in the ring form of the asexual blood stages of the parasite. The C-terminal catalytic domain of PfPDE1, produced in Escherichia coli, specifically hydrolysed cGMP with a Km value of 0.65 μM. Among the PDE inhibitors tested, a PDE5 inhibitor, zaprinast, was the most effective, having an IC50 value of 3.8 μM. The non-specific PDE inhibitors IBMX (3-isobutyl-1-methylxanthine), theophylline and the antimalarial chloroquine had IC50 values of over 100 μM. Membrane fractions prepared from P. falciparum at mixed asexual blood stages showed potent cGMP hydrolytic activity compared with cytosolic fractions. This hydrolytic activity was sensitive to zaprinast with an IC50 value of 4.1 μM, but insensitive to IBMX and theophylline. Furthermore, an in vitro antimalarial activity assay demonstrated that zaprinast inhibited the growth of the asexual blood parasites, with an ED50 value of 35 μM. The impact of cyclic nucleotide signalling on the cellular development of this parasite has previously been discussed. Thus this enzyme is suggested to be a novel potential target for the treatment of the disease malaria.

Sign in / Sign up

Export Citation Format

Share Document