scholarly journals Ligands of the Peripheral Benzodiazepine Receptor Are Potent Inhibitors of Plasmodium falciparum and Toxoplasma gondii In Vitro

2002 ◽  
Vol 46 (10) ◽  
pp. 3197-3207 ◽  
Author(s):  
Florence Dzierszinski ◽  
Alexandra Coppin ◽  
Marlene Mortuaire ◽  
Etienne Dewailly ◽  
Christian Slomianny ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Toxoplasma Gondii ◽  
Morphological Changes ◽  
Synergistic Effects ◽  
Benzodiazepine Receptor ◽  
Peripheral Benzodiazepine Receptor ◽  
Parasite Resistance ◽  
Antimalarial Agents ◽  
Parasite Replication

ABSTRACT The increase in resistance of the malaria parasite Plasmodium falciparum to currently available drugs demands the development of new antimalarial agents. In this quest, we have found that ligands to the peripheral benzodiazepine receptor such as flurazepam, an agonist of the benzodiazepine family, and PK11195, an antagonist derived from isoquinoline, were active against Plasmodium falciparum. These two compounds effectively and rapidly inhibited parasite growth in vitro, irrespective of parasite resistance to chloroquine and mefloquine. Treatment with both drugs induced a sharp and consistent decline in parasitemia, a complete inhibition of parasite replication, and the destruction of parasites within the host red blood cells. Using electron microscopy, we showed that dramatic morphological changes, involving swollen endoplasmic reticulum and the reduction of hemozoin, were consistent with parasite death. The potent activities of flurazepam and PK11195 were also evaluated for antagonist or synergistic effects with currently used antimalarial drugs such as chloroquine and mefloquine. Moreover, flurazepam was found to be active against Toxoplasma gondii, another member of the phylum Apicomplexa. Taken together, our results indicated that benzodiazepines could be considered promising candidates in the treatment of both malaria and toxoplasmosis.

scholarly journals Interaction of Plasmodium falciparum apicortin with α- and β-tubulin is critical for parasite growth and survival

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Malabika Chakrabarti ◽  
Nishant Joshi ◽  
Geeta Kumari ◽  
Preeti Singh ◽  
Rumaisha Shoaib ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Life Cycle ◽  
Specific Protein ◽  
Parasite Growth ◽  
Growth And Survival ◽  
Apicomplexan Parasites ◽  
Parasite Replication ◽  
Main Components ◽  
Β Tubulin

AbstractCytoskeletal structures of Apicomplexan parasites are important for parasite replication, motility, invasion to the host cell and survival. Apicortin, an Apicomplexan specific protein appears to be a crucial factor in maintaining stability of the parasite cytoskeletal assemblies. However, the function of apicortin, in terms of interaction with microtubules still remains elusive. Herein, we have attempted to elucidate the function of Plasmodium falciparum apicortin by monitoring its interaction with two main components of parasite microtubular structure, α-tubulin-I and β-tubulin through in silico and in vitro studies. Further, a p25 domain binding generic drug Tamoxifen (TMX), was used to disrupt PfApicortin-tubulin interactions which led to the inhibition in growth and progression of blood stage life cycle of P. falciparum.

scholarly journals Experimental conversion of virulent RH Toxoplasma gondii tachyzoites in vitro

2001 ◽  
Vol 7 (1-2) ◽  
pp. 181-188
Author(s):  
N. A. Hammouda ◽  
I. R. Ibrahim ◽  
E. D. Elkerdany ◽  
A. Y. Negm ◽  
S. R. Allam
Keyword(s):  
Toxoplasma Gondii ◽  
Culture Medium ◽  
Dna Analysis ◽  
Morphological Changes ◽  
Control Group ◽  
Image Analyser

We aimed to induce conversion of RH-stain tachyzoites to bradyzoites by changing the pH of the culture medium. Alkalization of the medium to pH 8 induced morphological changes in the cultured tachyzoites. The majority of the organism increased in size and changed from a regular crescent shape to a rounded or ovoid shape. Cyst-like structures were formed. Using a computerized image analyser, significant differences in the size of the whole organisms and in their nuclei were observed compared to the control group. The converted organisms also showed significant differences from the control group by quantitative DNA analysis, and did not infect mice.

Peripheral Benzodiazepine Receptor Antisense Knockout Increases Tumorigenicity of MA-10 Leydig Cells in Vivo and in Vitro†

Biochemistry ◽  
2004 ◽  
Vol 43 (38) ◽  
pp. 12315-12321 ◽  
Author(s):  
Gary Weisinger ◽  
Ela Kelly-Hershkovitz ◽  
Leo Veenman ◽  
Ilana Spanier ◽  
Svetlana Leschiner ◽  
...  
Keyword(s):  
Leydig Cells ◽  
Benzodiazepine Receptor ◽  
Peripheral Benzodiazepine Receptor

A Peripheral Benzodiazepine Receptor Targeted Agent for In Vitro Imaging and Screening

2006 ◽  
Vol 17 (3) ◽  
pp. 735-740 ◽  
Author(s):  
H. Charles Manning ◽  
Sarah M. Smith ◽  
Michelle Sexton ◽  
Sarah Haviland ◽  
Mingfeng Bai ◽  
...  
Keyword(s):  
Benzodiazepine Receptor ◽  
Peripheral Benzodiazepine Receptor ◽  
Targeted Agent

scholarly journals Inhibition of Toxoplasma gondii and Plasmodium falciparum Infections in Vitro by NSC3852, a Redox Active Antiproliferative and Tumor Cell Differentiation Agent

2009 ◽  
Vol 95 (1) ◽  
pp. 215-223 ◽  
Author(s):  
Jeannine S. Strobl ◽  
Christopher W. Seibert ◽  
Yunbo Li ◽  
Rana Nagarkatti ◽  
Sheila M. Mitchell ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Cell Differentiation ◽  
Toxoplasma Gondii ◽  
Tumor Cell ◽  
Redox Active ◽  
Tumor Cell Differentiation

scholarly journals Role of pfmdr1 Amplification and Expression in Induction of Resistance to Artemisinin Derivatives in Plasmodium falciparum

2010 ◽  
Vol 54 (6) ◽  
pp. 2455-2464 ◽  
Author(s):  
Marina Chavchich ◽  
Lucia Gerena ◽  
Jennifer Peters ◽  
Nanhua Chen ◽  
Qin Cheng ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Copy Number ◽  
Practical Importance ◽  
Parasite Resistance ◽  
Coding Sequences ◽  
Artemisinin Derivatives ◽  
Induction Of Resistance ◽  
Selection Of

ABSTRACT Artemisinin and its derivatives are the most rapidly acting and efficacious antimalarial drugs currently available. Although resistance to these drugs has not been documented, there is growing concern about the potential for resistance to develop. In this paper we report the selection of parasite resistance to artelinic acid (AL) and artemisinin (QHS) in vitro and the molecular changes that occurred during the selection. Exposure of three Plasmodium falciparum lines (W2, D6, and TM91C235) to AL resulted in decreases in parasite susceptibilities to AL and QHS, as well as to mefloquine, quinine, halofantrine, and lumefantrine. The changes in parasite susceptibility were accompanied by increases in the copy number, mRNA expression, and protein expression of the pfmdr1 gene in the resistant progenies of W2 and TM91C235 parasites but not in those of D6 parasites. No changes were detected in the coding sequences of the pfmdr1, pfcrt, pfatp6, pftctp, and pfubcth genes or in the expression levels of pfatp6 and pftctp. Our data demonstrate that P. falciparum lines have the capacity to develop resistance to artemisinin derivatives in vitro and that this resistance is achieved by multiple mechanisms, to include amplification and increased expression of pfmdr1, a mechanism that also confers resistance to mefloquine. This observation is of practical importance, because artemisinin drugs are often used in combination with mefloquine for the treatment of malaria.

scholarly journals Malaria prevalence and In vitro susceptibility of Plasmodium falciparum isolates to selected antimalarial agents in Bauchi, Nigeria

2020 ◽  
Vol 13 (6) ◽  
pp. 2714
Author(s):  
Awute David Atang ◽  
Jonathan Yusuf Azi ◽  
Faizah Oseze Sani ◽  
Rukayat Avosuahi Oyi ◽  
Joseph Olorunmola Ehinmidu
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Prevalence ◽  
In Vitro Susceptibility ◽  
Antimalarial Agents

scholarly journals A Novel Series of [1,2,4]Triazolo[4,3-a]Pyridine Sulfonamides as Potential Antimalarial Agents: In Silico Studies, Synthesis and In Vitro Evaluation

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4485
Author(s):  
Veronika R. Karpina ◽  
Svitlana S. Kovalenko ◽  
Sergiy M. Kovalenko ◽  
Oleksandr G. Drushlyak ◽  
Natalya D. Bunyatyan ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Docking ◽  
Virtual Screening ◽  
Inhibitory Concentration ◽  
Antimalarial Activity ◽  
Virtual Library ◽  
Antimalarial Agents ◽  
Starting Point ◽  
In Silico Studies

For the development of new and potent antimalarial drugs, we designed the virtual library with three points of randomization of novel [1,2,4]triazolo[4,3-a]pyridines bearing a sulfonamide fragment. The library of 1561 compounds has been investigated by both virtual screening and molecular docking methods using falcipain-2 as a target enzyme. 25 chosen hits were synthesized and evaluated for their antimalarial activity in vitro against Plasmodium falciparum. 3-Ethyl-N-(3-fluorobenzyl)-N-(4-methoxyphenyl)-[1,2,4]triazolo[4,3-a]pyridine-6-sulfonamide and 2-(3-chlorobenzyl)-8-(piperidin-1-ylsulfonyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one showed in vitro good antimalarial activity with inhibitory concentration IC50 = 2.24 and 4.98 μM, respectively. This new series of compounds may serve as a starting point for future antimalarial drug discovery programs.

scholarly journals Bisbenzylisoquinolines as modulators of chloroquine resistance in Plasmodium falciparum and multidrug resistance in tumor cells.

1996 ◽  
Vol 40 (6) ◽  
pp. 1476-1481 ◽  
Author(s):  
F Frappier ◽  
A Jossang ◽  
J Soudon ◽  
F Calvo ◽  
P Rasoanaivo ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Multidrug Resistance ◽  
Tumor Cells ◽  
Synergistic Effects ◽  
Cancer Cell Line ◽  
Multidrug Resistant ◽  
Chloroquine Resistance ◽  
Naturally Occurring ◽  
Structure Activity

Ten naturally occurring bisbenzylisoquinolines (BBIQ) and two dihydro derivatives belonging to five BBIQ subgroups were evaluated in vitro for their ability to inhibit Plasmodium falciparum growth and, in drug combination, to reverse the resistance to chloroquine of strain FcB1. The same alkaloids were also assessed in vitro for their potentiating activity against vinblastine with the multidrug-resistant clone CCRF-CEM/VLB, established from lymphoblastic acute leukemia. Three of the BBIQ tested had 50% inhibitory concentrations of less than 1 microM. The most potent antimalarial agent was cocsoline (50% inhibitory concentration, 0.22 microM). Regarding the chloroquine-potentiating effect, fangchinoline exhibited the highest biological activity whereas the remaining compounds displayed either antagonistic or slight synergistic effects. Against the multidrug-resistant cancer cell line, fangchinoline was also by far the most active compound. Although there were clear differences between the activities of tested alkaloids, no relevant structure-activity relationship could be established. Nevertheless, fangchinoline appears to be a new biochemical tool able to help in the comprehension of the mechanism of both chloroquine resistance in P. falciparum and multidrug resistance in tumor cells.

Sign in / Sign up

Export Citation Format

Share Document