Characterization of the effect of retinol on Plasmodium falciparum in vitro

2004 ◽  
Vol 107 (3-4) ◽  
pp. 136-144 ◽  
Author(s):  
J. Hamzah ◽  
T.M.E. Davis ◽  
T.S. Skinner-Adams ◽  
J. Beilby
Keyword(s):  
Plasmodium Falciparum

scholarly journals Sintesis dan Evaluasi Antimalaria In Vitro Turunan Kinin Terhadap Plasmodium falciparum

2021 ◽  
Vol 11 (2) ◽  
pp. 109-120
Author(s):  
Salahuddin Salahuddin ◽  
Rahmana Emran K ◽  
Muhammad Hanafi ◽  
Andini Sundowo ◽  
Puspa Dewi NL ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Antimalarial Drug ◽  
Malaria Treatment ◽  
Reaction Products ◽  
Synthetic Product ◽  
13C Nuclear Magnetic Resonance ◽  
Ic50 Value ◽  
Ic50 Values

Nowadays kinin is the most effective antimalarial drug and its used as an alternative in malaria treatment. However, toxicity of quinine restrict its use as an antimalarial drug. Lipophilicity and long half-life (t½) of quinine that reach 10-20 hours are responsible for its toxicity. The aim of this research is to obtain more polar quinine derivatives by means of hydrogen peroxide reactions to reduce the toxicity. The reactions using hydrogen peroxyde is performed analogously to the procedures reported in the literature. Extract of pure anhydrous kinin is purified in coloumn chromatography followed by structure elucidation. Synthetic product is tested in vitro against Plasmodium falciparum. The characterization of reaction products is performed with proton (1H) and carbon 13 (13C) nuclear magnetic resonance (NMR) spectroscopy. It showed that the reaction using reagents led to epoxidation of vinyl substituents of chinuclidine ring with 61,08% yields. Antimalarial test against Plasmodium falciparum obtained 1.250-2.500 μg/mL of IC50 value. The IC50 values indicated that the synthesis products were not potential for malaria treatment.

scholarly journals Detailed characterization of a cyclophilin from the human malaria parasite Plasmodium falciparum

1998 ◽  
Vol 334 (2) ◽  
pp. 437-445 ◽  
Author(s):  
Matthew BERRIMAN ◽  
Alan H. FAIRLAMB
Keyword(s):  
Plasmodium Falciparum ◽  
Antimalarial Activity ◽  
Functional Characterization ◽  
Gene Encoding ◽  
Isomerase Activity ◽  
Downstream Target ◽  
Parasite Plasmodium Falciparum

Cyclosporin (Cs) A has pronounced antimalarial activity in vitro and in vivo. In other organisms, the drug is thought to exert its effects either by inhibiting the peptidylprolyl cis/trans isomerase activity of cyclophilin (CyP) or by forming a CyP–CsA complex that inhibits the phosphatase activity of calcineurin. We have cloned and overexpressed in Escherichia coli a gene encoding a CyP from Plasmodium falciparum (PfCyP19) that is located on chromosome 3. The sequence of PfCyP19 shows remarkable sequence identity with human CyPA and, unlike the two previously identified CyPs from P. falciparum, PfCyP19 has no signal peptide or N-terminal sequence extension, suggesting a cytosolic localization. All the residues implicated in the recognition of the synthetic substrate N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide are conserved, resulting in characteristically high Michaelis–Menten and specificity constants (Km ≫ 120 µM, kcat/Km = 1.2×107 M-1·s-1 respectively). As the first line in the functional characterization of this enzyme, we have assessed its binding affinity for CsA. In accordance with its tryptophan-containing CsA-binding domain, PfCyP19 binds CsA with high affinity (Kd = 13 nM, Ki = 6.9 nM). Twelve CsA analogues were also found to possess Ki values similar to CsA, with the notable exceptions of Val2-Cs (Ki = 218 nM) and Thr2-Cs (Ki = 690 nM). The immunosuppressants rapamycin and FK506 were inactive as inhibitors, consistent with other members of the CyP family of rotamases. The CsA analogues were also assessed as inhibitors of P. falciparum growth in vitro. Although their antimalarial activity did not correlate with inhibition of enzyme activity, residues 3 and 4 of CsA appeared to be important for inhibition of parasite growth and residues 1 and 2 for PfCyP19 inhibition. We propose that a malarial CyP–CsA complex presents residues 3 and 4 as part of an ‘effector surface ’ for recognition by a downstream target, similar to the proposed mechanism for T-cell immunosuppression.

scholarly journals pfcrt Polymorphism and Chloroquine Resistance in Plasmodium falciparum Strains Isolated in Cambodia

2003 ◽  
Vol 47 (1) ◽  
pp. 87-94 ◽  
Author(s):  
Pharath Lim ◽  
Sophy Chy ◽  
Frédéric Ariey ◽  
Sandra Incardona ◽  
Pektra Chim ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Geographical Origin ◽  
Point Mutations ◽  
Chloroquine Resistance ◽  
Allelic Form ◽  
Eastern Province

ABSTRACT Plasmodium falciparum chloroquine resistance was first detected in Cambodia in the early sixties. Treatment with chloroquine was abandoned 20 years ago. In vitro chloroquine sensitivity monitoring indicates that all eastern Cambodian isolates were sensitive to chloroquine, whereas most isolates collected from western provinces displayed reduced susceptibility to chloroquine. This indicates that the rate of chloroquine resistance remains high and stable in this region in the absence of chloroquine pressure. Characterization of codons 72 to 78 and 218 to 220 of pfcrt revealed six distinct haplotypes, four of which had never been described. The frequency of each haplotype depended on the geographical origin of the samples. The CVIETIF//ISS haplotype was detected in 92% of western Cambodian isolates and in 11% of isolates collected from the eastern province, where CVMNKIF//ISA and CVIDTIF//ISS predominate. The detection of an intermediate haplotype from a susceptible area with 76T/220A, suggests that acquisition of chloroquine resistance might be a stepwise process, during which accumulation of point mutations modulates the response to chloroquine. The association of the K76T mutation with chloroquine resistance was not clear. The mutation was detected in resistant and susceptible samples, suggesting that additional factors are involved in chloroquine resistance. By contrast, the pfcrt D/N75E mutation was strongly associated with the in vitro chloroquine resistance in Cambodian isolates. The N86 allelic form of pfmdr1 was detected in all isolates, consistent with a poor association with resistance to chloroquine. This indicates that in vitro resistance to chloroquine was associated with accumulation of point mutations in pfcrt.

scholarly journals Cholesterol bound Plasmodium falciparum co-chaperone ‘PFA0660w’ complexes with major virulence factor ‘PfEMP1’ via chaperone ‘PfHsp70-x’

2018 ◽  
Author(s):  
Ankita Behl ◽  
Vikash Kumar ◽  
Anjali Bisht ◽  
Jiban J. Panda ◽  
Rachna Hora ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Direct Interaction ◽  
Lipid Binding ◽  
The Novel ◽  
The Past ◽  
Biochemical Assays ◽  
Erythrocyte Surface ◽  
Parasite Survival

AbstractLethality of Plasmodium falciparum (Pf) caused malaria results from ‘cytoadherence’, which is effected by exported Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family. Several exported Pf proteins (exportome) including chaperones alongside cholesterol rich microdomains are crucial for PfEMP1 translocation to infected erythrocyte surface. An exported Hsp40 (heat shock protein 40) ‘PFA0660w’ functions as a co-chaperone of ‘PfHsp70-x’, and these co-localize to specialized intracellular mobile structures termed J-dots. Our studies attempt to understand the function of PFA0660w-PfHsp70-x chaperone pair using recombinant proteins. Biochemical assays reveal that N and C-terminal domains of PFA0660w and PfHsp70-x respectively are critical for their activity. We show the novel direct interaction of PfHsp70-x with the cytoplasmic tail of PfEMP1, and binding of PFA0660w with cholesterol. PFA0660w operates both as a chaperone and lipid binding molecule via its separate substrate and cholesterol binding sites. PfHsp70-x binds cholesterol linked PFA0660w and PfEMP1 simultaneously in vitro to form a complex. Collectively, our results and the past literature support the hypothesis that PFA0660w-PfHsp70-x chaperone pair assists PfEMP1 transport across the host erythrocyte through cholesterol containing ‘J-dots’. Since PFA0660w seems essential for parasite survival, characterization of its interaction with PfHsp70-x and J-dots may form the basis for development of future antimalarials.

Investigation of Antiplasmodial Effects of Terpenoid Compounds Isolated from Myrrh

Planta Medica ◽  
2020 ◽  
Vol 86 (09) ◽  
pp. 643-654 ◽  
Author(s):  
Hippolyt L. Greve ◽  
Marcel Kaiser ◽  
Thomas J. Schmidt
Keyword(s):  
Plasmodium Falciparum ◽  
In Vitro Activity ◽  
Isolation And Characterization ◽  
Spectroscopic Analyses ◽  
Ic50 Value ◽  
Ic50 Values ◽  
O 18 ◽  
First Time

AbstractAs part of our ongoing search for antiprotozoal natural products from plants, we examined different resins from the Burseraceae family. The dichloromethane extract obtained from myrrh, the oleo-gum-resin of Commiphora species, showed promising in vitro activity against Plasmodium falciparum with an IC50 value of 1 µg/mL. Bioactivity-guided fractionation led to the isolation and characterization of 18 sesquiterpenoids, namely, β-elemene (1), elemyl acetate (2), curzerenone (3), 8-hydroxyisogermafurenolide (4), 2-methoxyisogermafurenolide (5), 8-epi-2-methoxyisogermafurenolide (6), furanodienone (7), 1(10)Z,4Z-furanodien-6-one (8), rel-2R-methyl-5S-acetoxy-4R-furanogermacr-1(10)Z-en-6-one (9), (1(10)E)-2-methoxy-8,12-epoxygermacra-1(10),7,11-trien-6-one (10), 2R-methoxyfuranodiene (11), 2-acetyloxyglechomanolide (12), 8-epi-2-acetyloxyglechomanolide (13), (1R,2R,4S)-1,2-epoxyfuranogermacr-10(15)-en-6-one (14), hydroxylindestrenolide (15), isohydroxylindestrenolide (16), myrrhone (17), and myrrhterpenoid O (18). Moreover, nine (nor-)triterpenoids were isolated: mansumbinol (19), mansumbinol epoxide (20), mansumbinone (21), mansumbin-13(17)-en-3,16-dione (22), 3,4-seco-mansumbinoic acid (23), rel-20S-hydroxy-dammar-24-en-3,16-dione (24), rel-(16S,20S)-dihydroxydammar-24-en-3-one (25), cycloart-24-en-1α,2α,3β-triol (26), and 3β-isovaleroyloxycycloart-24-en-1α,2α-diol (27). All compounds were identified by MS and NMR spectroscopic analyses. To the best of our knowledge, compounds 5, 6, 12, 13, 16, 18, and 20 are reported for the first time. All isolated compounds were tested in vitro for activity against P. falciparum and cytotoxicity. The sesquiterpene 7 and the triterpene 25 were the most active compounds found in this study with IC50 values of 7.4 and 2.8 µM, respectively.

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