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in vitro

Effects of combined drug treatments on Plasmodium falciparum: In vitro assays with doxycycline, ivermectin and efflux pump inhibitors

April 27, 2020 - 12:53 -- Open Access
Nodari R, Corbett Y, Varotto-Boccazzi I, Porretta D, Taramelli D, Epis S, Bandi C
PLoS ONE 15(4): e0232171

There is great concern regarding the rapid emergence and spread of drug-resistance in Plasmodium falciparum, the parasite responsible for the most severe form of human malaria. Parasite populations resistant to some or all the currently available antimalarial treatments are present in different world regions. Considering the need for novel and integrated approaches to control malaria, combinations of drugs were tested on P. falciparum. The primary focus was on doxycycline, an antibiotic that specifically targets the apicoplast of the parasite.

NOT Open Access | The in vitro antiplasmodial and antiproliferative activity of new ferrocene-based α-aminocresols targeting hemozoin inhibition and DNA interaction

April 21, 2020 - 13:26 -- NOT Open Access
Mbaba M, Dingle LMK, Swart T, Cash D, Laming D, de la Mare JA, Taylor D, Hoppe HC, Biot C, Edkins AL, Khanye SD
Chembiochem. 2020 Apr 19

Conjugation of organometallic complexes to known bioactive organic frameworks is a proven strategy revered for devising new drug molecules with novel modes of action. Herein, we present the in vitro antimalarial and antiproliferative investigation of ferrocenyl α‐aminocresol conjugates assembled by amalgamation of the organometallic ferrocene unit and the α‐aminocresol scaffold.

In Vitro Activities of MMV Malaria Box Compounds against the Apicomplexan Parasite Neospora caninum, the Causative Agent of Neosporosis in Animals

March 30, 2020 - 10:15 -- Open Access
Müller J, Winzer PA, Samby K, Hemphill A
Molecules. 2020 Mar 24;25(6). pii: E1460

Neospora caninum is a major cause of abortion in cattle and represents a veterinary health problem of great economic significance. In order to identify novel chemotherapeutic agents for the treatment of neosporosis, the Medicines for Malaria Venture (MMV) Malaria Box, a unique collection of anti-malarial compounds, were screened against N. caninum tachyzoites, and the most efficient compounds were characterized in more detail.

Detection of the in vitro modulation of Plasmodium falciparum Arf1 by Sec7 and ArfGAP domains using a colorimetric plate-based assay

March 17, 2020 - 12:47 -- Open Access
Swart T, Khan FD, Ntlantsana A, Laming D, Veale CGL, Przyborski JM, Edkins AL, Hoppe HC
Sci Rep. 2020 Mar 6; 10(1):4193

The regulation of human Arf1 GTPase activity by ArfGEFs that stimulate GDP/GTP exchange and ArfGAPs that mediate GTP hydrolysis has attracted attention for the discovery of Arf1 inhibitors as potential anti-cancer agents. The malaria parasite Plasmodium falciparum encodes a Sec7 domain-containing protein - presumably an ArfGEF - and two putative ArfGAPs, as well as an Arf1 homologue (PfArf1) that is essential for blood-stage parasite viability.

NOT Open Access | Novel Chloroquine Loaded Curcumin Based Anionic Linear Globular Dendrimer G2: A metabolomics study on Plasmodium falciparum in vitro using 1HNMR spectroscopy

March 3, 2020 - 12:32 -- NOT Open Access
Elmi T, Ardestani MS, Hajialiani F, Motevalian M, Mohamadi M, Sadeghi S, Zamani Z, Tabatabaie F
Parasitology, February 2020, pp. 1-40

No abstract available

NOT Open Access | In vitro screening of the open source MMV Malaria and Pathogen Boxes to discover novel compounds with activity against Balamuthia mandrillaris

February 24, 2020 - 14:00 -- NOT Open Access
Rice CA, Lares-Jiménez LF, Lares-Villa F, Kyle DE
Antimicrob Agents Chemother. 2020 Feb 18. pii: AAC.02233-19

Balamuthia mandrillaris, is an under reported pathogenic free-living amoeba that causes Balamuthia amoebic encephalitis (BAE) and cutaneous skin infections. Although cutaneous infections are not typically lethal, BAE with or without cutaneous involvement usually is fatal. This is due to lack of drugs that are efficacious and that can cross the blood-brain barrier. We aimed to discover new leads for drug discovery by screening the open source MMV Malaria and MMV Pathogen boxes (800 compounds total).

Vaccination with virosomally formulated recombinant CyRPA elicits protective antibodies against Plasmodium falciparum parasites in preclinical in vitro and in vivo models

February 11, 2020 - 16:23 -- Open Access
Marco Tamborrini, Julia Hauser, Anja Schäfer, Mario Amacker, Paola Favuzza, Kwak Kyungtak, Sylvain Fleury, Gerd Pluschke
NPJ Vaccines. 2020; 5:9

The Plasmodium falciparum (Pf) cysteine-rich protective antigen (PfCyRPA) has emerged as a promising blood-stage candidate antigen for inclusion into a broadly cross-reactive malaria vaccine. This highly conserved protein among various geographical strains plays a key role in the red blood cell invasion process by P. falciparum merozoites, and antibodies against PfCyRPA can efficiently prevent the entry of the malaria parasites into red blood cells.

Sexual forms obtained in a continuous in vitro cultured Colombian strain of Plasmodium falciparum (FCB2)

February 10, 2020 - 16:03 -- Open Access
Monica Ararat-Sarria, Cesar Camilo Prado, Milena Camargo, Laura Tatiana Ospina, Paola Andrea Camargo, Hernando Curtidor and Manuel Alfonso Patarroyo
Malaria Journal 2020 19:57, 3 February 2020

The epidemiological control of malaria has been hampered by the appearance of parasite resistance to anti-malarial drugs and by the resistance of mosquito vectors to control measures. This has also been associated with weak transmission control, mostly due to poor control of asymptomatic patients associated with host-vector transmission. This highlights the importance of studying the parasite’s sexual forms (gametocytes) which are involved in this phase of the parasite’s life-cycle. Some African and Asian strains of Plasmodium falciparum have been fully characterized regarding sexual forms’ production; however, few Latin-American strains have been so characterized. This study was aimed at characterizing the Colombian FCB2 strain as a gametocyte producer able to infect mosquitoes.

A dual fluorescent Plasmodium cynomolgi reporter line reveals in vitro malaria hypnozoite reactivation

January 14, 2020 - 12:14 -- Open Access
Voorberg-van der Wel AM, Zeeman AM, Kocken CHM, et al.
Communications Biology, 2020 Jan 3; 3:7

Plasmodium vivax malaria is characterized by repeated episodes of blood stage infection (relapses) resulting from activation of dormant stages in the liver, so-called hypnozoites. Transition of hypnozoites into developing schizonts has never been observed. A barrier for studying this has been the lack of a system in which to monitor growth of liver stages.

NOT Open Access | Modification of pfap2μ and pfubp1 Markedly Reduces Ring-Stage Susceptibility of Plasmodium falciparum to Artemisinin In Vitro

December 23, 2019 - 16:02 -- NOT Open Access
Henrici RC, van Schalkwyk DA, Sutherland CJ
Antimicrob Agents Chemother. 2019 Dec 20;64(1). pii: e01542-19

Management of uncomplicated malaria worldwide is threatened by the emergence in Asia of Plasmodium falciparum carrying variants of the pfk13 locus and exhibiting reduced susceptibility to artemisinin. Mutations in two other genes, ubp1 and ap2μ, are associated with artemisinin resistance in rodent malaria and with clinical failure of combination therapy in African malaria patients. Transgenic P. falciparum clones, each carrying orthologues of mutations in pfap2μ and pfubp1 associated with artemisinin resistance in Plasmodium chabaudi, were derived by Cas9 gene editing.


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