scholarly journals Peptide Inhibition of Topoisomerase IB from Plasmodium falciparum

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Amit Roy ◽  
Ilda D'Annessa ◽  
Christine J. F. Nielsen ◽  
David Tordrup ◽  
Rune R. Laursen ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Topoisomerase I ◽  
Mechanistic Explanation ◽  
Inhibitory Effect ◽  
Drug Resistant ◽  
Protozoan Parasites ◽  
New Class ◽  
Topoisomerase Ib ◽  
Essential Enzyme ◽  
Ligation Step

Control of diseases inflicted by protozoan parasites such as Leishmania, Trypanosoma, and Plasmodium, which pose a serious threat to human health worldwide, depends on a rather small number of antiparasite drugs, of which many are toxic and/or inefficient. Moreover, the increasing occurrence of drug-resistant parasites emphasizes the need for new and effective antiprotozoan drugs. In the current study, we describe a synthetic peptide, WRWYCRCK, with inhibitory effect on the essential enzyme topoisomerase I from the malaria-causing parasite Plasmodium falciparum. The peptide inhibits specifically the transition from noncovalent to covalent DNA binding of P. falciparum topoisomerase I, while it does not affect the ligation step of catalysis. A mechanistic explanation for this inhibition is provided by molecular docking analyses. Taken together the presented results suggest that synthetic peptides may represent a new class of potential antiprotozoan drugs.

scholarly journals Stage-dependent effect of deferoxamine on growth of Plasmodium falciparum in vitro

Blood ◽  
1990 ◽  
Vol 76 (6) ◽  
pp. 1250-1255 ◽  
Author(s):  
S Whitehead ◽  
TE Peto
Keyword(s):  
Plasmodium Falciparum ◽  
Growth Inhibition ◽  
Antimalarial Activity ◽  
Clinical Malaria ◽  
Inhibitory Effect ◽  
Parasite Development ◽  
And Control ◽  
Speed Of Onset

Abstract Deferoxamine (DF) has antimalarial activity that can be demonstrated in vitro and in vivo. This study is designed to examine the speed of onset and stage dependency of growth inhibition by DF and to determine whether its antimalarial activity is cytostatic or cytocidal. Growth inhibition was assessed by suppression of hypoxanthine incorporation and differences in morphologic appearance between treated and control parasites. Using synchronized in vitro cultures of Plasmodium falciparum, growth inhibition by DF was detected within a single parasite cycle. Ring and nonpigmented trophozoite stages were sensitive to the inhibitory effect of DF but cytostatic antimalarial activity was suggested by evidence of parasite recovery in later cycles. However, profound growth inhibition, with no evidence of subsequent recovery, occurred when pigmented trophozoites and early schizonts were exposed to DF. At this stage in parasite development, the activity of DF was cytocidal and furthermore, the critical period of exposure may be as short as 6 hours. These observations suggest that iron chelators may have a role in the treatment of clinical malaria.

scholarly journals Predictors of treatment failures of plasmodium falciparum malaria in Vietnam: a 4-year single‐centre retrospective study

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Minh Cuong Duong ◽  
Oanh Kieu Nguyet Pham ◽  
Phong Thanh Nguyen ◽  
Van Vinh Chau Nguyen ◽  
Phu Hoan Nguyen
Keyword(s):  
Plasmodium Falciparum ◽  
Treatment Failure ◽  
Severe Malaria ◽  
Falciparum Malaria ◽  
Control Strategies ◽  
Artemisinin Resistance ◽  
Plasmodium Falciparum Malaria ◽  
Molecular Technique ◽  
Drug Resistant ◽  
Public Health Burden

Abstract Background Drug-resistant falciparum malaria is an increasing public health burden. This study examined the magnitude of Plasmodium falciparum infection and the patterns and predictors of treatment failure in Vietnam. Methods Medical records of all 443 patients with malaria infection admitted to the Hospital for Tropical Diseases between January 2015 and December 2018 were used to extract information on demographics, risk factors, symptoms, laboratory tests, treatment, and outcome. Results More than half (59.8%, 265/443, CI 55.1–64.4%) of patients acquired Plasmodium falciparum infection of whom 21.9% (58/265, CI 17.1–27.4%) had severe malaria, while 7.2% (19/265, CI 4.6–10.9%) and 19.2% (51/265, CI 14.7–24.5%) developed early treatment failure (ETF) and late treatment failure (LTF) respectively. Among 58 patients with severe malaria, 14 (24.1%) acquired infection in regions where artemisinin resistance has been documented including Binh Phuoc (11 patients), Dak Nong (2 patients) and Gia Lai (1 patient). Under treatment with intravenous artesunate, the median (IQR) parasite half-life of 11 patients coming from Binh Phuoc was 3 h (2.3 to 8.3 h), two patients coming from Dak Nong was 2.8 and 5.7 h, and a patient coming from Gia Lai was 6.5 h. Most patients (98.5%, 261/265) recovered completely. Four patients with severe malaria died. Severe malaria was statistically associated with receiving treatment at previous hospitals (P < 0.001), hepatomegaly (P < 0.001) and number of inpatient days (P < 0.001). Having severe malaria was a predictor of ETF (AOR 6.96, CI 2.55–19.02, P < 0.001). No predictor of LTF was identified. Conclusions Plasmodium falciparum remains the prevalent malaria parasite. Despite low mortality rate, severe malaria is not rare and is a significant predictor of ETF. To reduce the risk for ETF, studies are needed to examine the effectiveness of combination therapy including parenteral artesunate and a parenteral partner drug for severe malaria. The study alerts the possibility of drug-resistant malaria in Africa and other areas in Vietnam, which are known as non-endemic areas of anti-malarial drug resistance. A more comprehensive study using molecular technique in these regions is required to completely understand the magnitude of drug-resistant malaria and to design appropriate control strategies.

3-Hydroxy-propanamidines, a New Class of Orally Active Antimalarials Targeting Plasmodium falciparum

2021 ◽  
Vol 64 (6) ◽  
pp. 3035-3047
Author(s):  
Tanja C. Knaab ◽  
Jana Held ◽  
Bjoern B. Burckhardt ◽  
Kelly Rubiano ◽  
John Okombo ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
New Class ◽  
Orally Active

Robenidine Analogues Are Potent Antimalarials in Drug-Resistant Plasmodium falciparum

2021 ◽  
Author(s):  
Alina Krollenbrock ◽  
Yuexin Li ◽  
Jane Xu Kelly ◽  
Michael K. Riscoe
Keyword(s):  
Plasmodium Falciparum ◽  
Drug Resistant

scholarly journals Easy-To-Access Quinolone Derivatives Exhibiting Antibacterial and Anti-Parasitic Activities

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1141
Author(s):  
Richard M. Beteck ◽  
Audrey Jordaan ◽  
Ronnett Seldon ◽  
Dustin Laming ◽  
Heinrich C. Hoppe ◽  
...  
Keyword(s):  
Cell Wall ◽  
Protozoan Parasites ◽  
Trypanosoma Brucei Brucei ◽  
New Class ◽  
High Lipid ◽  
Host Infection ◽  
Eskape Pathogens ◽  
Quinolone Derivatives ◽  
Lipophilic Character

The cell wall of Mycobacterium tuberculosis (Mtb) has a unique structural organisation, comprising a high lipid content mixed with polysaccharides. This makes cell wall a formidable barrier impermeable to hydrophilic agents. In addition, during host infection, Mtb resides in macrophages within avascular necrotic granulomas and cavities, which shield the bacterium from the action of most antibiotics. To overcome these protective barriers, a new class of anti-TB agents exhibiting lipophilic character have been recommended by various reports in literature. Herein, a series of lipophilic heterocyclic quinolone compounds was synthesised and evaluated in vitro against pMSp12::GFP strain of Mtb, two protozoan parasites (Plasmodium falciparum and Trypanosoma brucei brucei) and against ESKAPE pathogens. The resultant compounds exhibited varied anti-Mtb activity with MIC90 values in the range of 0.24–31 µM. Cross-screening against P. falciparum and T.b. brucei, identified several compounds with antiprotozoal activities in the range of 0.4–20 µM. Compounds were generally inactive against ESKAPE pathogens, with only compounds 8c, 8g and 13 exhibiting moderate to poor activity against S. aureus and A. baumannii.

DRUG RESISTANT STRAINS OF PLASMODIUM FALCIPARUM IN PAPUA NEW GUINEA

The Lancet ◽  
1981 ◽  
Vol 317 (8216) ◽  
pp. 386
Author(s):  
Brian Darlow ◽  
Helena Vrbova ◽  
John Stace ◽  
Peter Heywood ◽  
Michael Alpers
Keyword(s):  
Plasmodium Falciparum ◽  
Papua New Guinea ◽  
New Guinea ◽  
Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

scholarly journals Enhanced Antibacterial Activity of Meropenem against Extensively Drug-Resistant Acinetobacter baumannii by Myrtaceae Plant Extracts

2020 ◽  
Vol 17 (11) ◽  
pp. 1168-1176
Author(s):  
Dennapa SAELOH ◽  
Monton VISUTTHI ◽  
Marisa LEEHA ◽  
Surasak LIMSUWAN ◽  
Supayang Piyawan VORAVUTHIKUNCHAI
Keyword(s):  
Acinetobacter Baumannii ◽  
Bacterial Infections ◽  
Inhibitory Concentration ◽  
Inhibitory Effect ◽  
Drug Resistant ◽  
Microdilution Method ◽  
Extensively Drug Resistant ◽  
Resistant Phenotype ◽  
Bacterial Growth Inhibition ◽  
Mic Value

Acinetobacter baumannii (A. baumannii) has been known as a major cause of nosocomial bacterial infections worldwide. The bacteria are increasingly associated with a broad spectrum of antibiotic resistance, and this has become a widespread concern in a variety of hospitals.Antibiotic development and alternative treatment have become priorities for the treatment of bacterial infections.This study investigated the efficacy of meropenem in combination with five ethanolic extracts of plants in Myrtaceae against extensively drug-resistant (XDR) A. baumannii. The resistant phenotype was previously determined by microdilution method. XDR-A. baumannii strains showed resistance to meropenem with the minimum inhibitory concentration (MIC) in a range of 16 - 128 µg/mL, whereas the MIC value of all extracts, including Calistemon lancealatus, Eucalyptus citridora, Rhodomytus tomentasa, Syzygium cumini, and Xanthortemon chrysanthus, was over 1,000 µg/mL. Interestingly, all extracts potentiated the activity of the antibiotic by reducing the MIC values of the antibiotic. Xanthortemon chrysanthus extract displayed excellent synergism against the bacteria by decreasing the MIC value of the drug greater than 8-fold. In addition, the extract, at concentrations of 31.25, 62.5, 125, 250, 500, and 1,000 µg/mL, obviously increased the inhibitory effect of meropenem (1/4´MIC) against A. baumannii. The percentage of bacterial growth inhibition by combination was 87.9, 88.8, 91.8, 93.6, 99.9, and 100, respectively. The results supported that the extract could improve the activity of ineffective antibiotics against drug-resistant pathogens.Therefore, the findings may serve as therapeutic options for XDR-A. baumannii infections in the future.

scholarly journals Anti-malarial plants in Ethiopia and their activities on drug resistant malaria

FEMS Microbes ◽  
2022 ◽  
Author(s):  
Yimeslal Atnafu Sema ◽  
Teshale Areda Waktola
Keyword(s):  
Plasmodium Falciparum ◽  
Medicinal Plants ◽  
Allium Sativum ◽  
Plasmodium Species ◽  
Drug Resistant ◽  
Effective Activity ◽  
Croton Macrostachyus ◽  
Phytochemical Constituents ◽  
Malaria Containment ◽  
Low Malaria Transmission

Abstract In Ethiopia, the impacts of malaria continue to cause a many number of morbidity and mortality that accounts to most outpatient observations. Ethiopia recently designed to attain nationwide malaria control by 2030 by beginning sub-national elimination in districts with low malaria transmission. However, the rises of drug-resistant parasites, especially Plasmodium falciparum hinder the malaria containment strategies. Plasmodium falciparum and Plasmodium vivax, dispersed all over the Ethiopia and accounting for 60% and 40% of malaria cases respectively. The aim of this report was to overview the phytochemical constituents, diversity and effect of some compound extracts on drug resistant plasmodium species. Many plant species, a total 200 identified by 82 studies, are used in traditional malaria treatments throughout the country. Allium sativum, Croton macrostachyus and Carica papaya were the more frequently used medicinal plants species. There are so many phytochemicals constituents found in medicinal plants used to treat malaria. Alkaloids, Flavonoids, Phenolics, Terpenoid and Glycosides are the most reported for their effective activity on drug resistant malaria.

scholarly journals Inhibitory Effect of Active Substances of Lollyfish (Holothuria atra) Against the Development of Plasmodium falciparum Based on In Silico Study

2020 ◽  
Vol 25 (4) ◽  
pp. 135-142
Author(s):  
Felly Moelyadi ◽  
Prawesty Diah Utami ◽  
Irmawati M. Dikman
Keyword(s):  
Plasmodium Falciparum ◽  
Antimalarial Drug ◽  
In Silico ◽  
Lethal Dose ◽  
Artemisinin Resistance ◽  
Inhibitory Effect ◽  
In Silico Study ◽  
Carbon Dioxide Co2 ◽  
Holothuria Atra ◽  
Active Substances

The high level of artemisinin resistance as the antimalarial drug makes the active substances found of lollyfish (Holothuria atra) become a very useful discovery as a new antimalarial drug. The purpose of this research is to find out the inhibitory effect of the active substances of lollyfish against the development of Plasmodium falciparum with in silico method. This is a one-shot experimental study research. Based on the test of potentially active substances of lollyfish through PubChem (https://pubchem.ncbi.nlm.nih.gov/), there are pyrogallol and catechin that have potential as the antimalarial drug. Pyrogallol, chlorogenic acid, catechin dan ascorbic acid have indirect inhibition to P. falciparum Orotidine 5-Monophosphate Decarboxylase (PfOMPDC) through carbon dioxide (CO2) and it is visualized by STITCH DB Version 5.0 (http://stitch.embl.de/). The binding affinity score of catechin, obtained from molecular docking, is higher than other substances and artemisinin. The Physicochemical and pharmacokinetic activity of the substance was predicted through SWISS ADME (http://www.swissadme.ch/index.php), while the toxicity was predicted through Pro-Tox (http://tox.charite.de/protox_II/). Catechin is a substance in lollyfish that is the safest because its lowest toxicity and very effective to be used as the antimalarial drug because of its high lethal dose 50 (LD50). Therefore, active substances in lollyfish have inhibitory effects against the development of P. falciparum based on in silico study.

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