scholarly journals Induction of Artesunate Resistance in Plasmodium Falciparum 3D7 Strain Using Intermittent Exposure Method and Comparing P.fk13 Sequence between Susceptible and Resistant Strains

2021 ◽  
Author(s):  
Sahar Barati ◽  
Afsaneh Motevalli Haghi ◽  
Mehdi Nateghpour ◽  
Zahra Zamani ◽  
Sadegh Khodaveisi ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Resistant Strain ◽  
Gene Sequence ◽  
Artemisinin Combination Therapy ◽  
Lethal Dose ◽  
Reduction Process ◽  
Intermittent Exposure ◽  
The World ◽  
Exposure Method ◽  
Resistant Strains

Abstract Background: Malaria is a major health issues in a number of countries in the world, especially tropical countries. Over the past 50 years, the resistance of Plasmodium falciparum has expanded against the antimalarial drugs that had been used to treat the disease. Recently resistance to some derivatives of artemisinin and the failure of artemisinin combination therapy (ACT) has threatened all major achievements in malaria control. Resistant strains are limited around the world, but it may spread very soon, hence the necessary to be prepared for any event regarding this matter, it is needed to organize more investigations about resistant strains and related genes. Preparation of a new resistant strain in the laboratory can provide opportunity to predict genes responsible for resistance. The aim of this study was to induce resistance to artesunate in Plasmodium falciparum 3D7 strain using intermittent exposure method and comparing P.fk13 gene sequence between susceptible and resistance strains.Methods: Plasmodium falciparum 3D7 strain was cultured according to Trager & Jensen method with some modifications. Serial concentrations between 10-2 mol/l, to 10-7mol/l were prepared, then P.falciparum 3D7 was exposed to each of the dilution to determine IC50 and lethal dose. After 24 hours exposure the rate of parasitemia and mean of growth inhibitory percent were evaluated. Sensitivity reduction process was started from the concentration of 10-7mol/l and ended at 10-2mol/l. Exposed parasites were collected after at least 27 days after cultivation in each drug concentration. DNA extraction, PCR and sequencing process were performed to investigate any possible mutations in the pfk13 gene sequence.Results: Effectiveness of 10-2mol/l concentration of artemisinin was found as a lethal dose. The resistant strain was provided in the lab, sequenced and registered in the gene bank as P.f Art -2, (accession number MH796123. 1). Alignment of this registered sample showed no mutation in P.f kelch13 gene in comparison with standard strain submitted in the Genebank. Conclusions: Results of this study showed that resistance to artesunate in malaria parasite may occur but with no mutation in the P.f kelch13 gene. Therefore, whole genome sequencing should be applied to determine mutations in resistant strains.

Synthesis, antitrypanosomal and antimycobacterial activities of coumarinic N-acylhydrazonic derivatives

2020 ◽  
Vol 16 ◽  
Author(s):  
Camila Capelini ◽  
Vitória R. F. Câmara ◽  
José D. Figueroa Villar ◽  
Juliana M. C. Barbosa ◽  
Kelly Salomão ◽  
...  
Keyword(s):  
Resistant Strain ◽  
Sensitive Strain ◽  
Moderate Activity ◽  
Active Compounds ◽  
Meaningful Activity ◽  
The World ◽  
Resistant Strains ◽  
Vitro Effect ◽  
Tuberculosis Activity

Background: Near to 5-7 million people are infected with T. cruzi in the world, and about 10,000 people per year die of problems associated to this disease. Method: We reported herein the synthesis, antitrypanosomal and antimycobacterial activities of seventeen coumarinic N-acylhydrazonic derivatives. Results: These compounds were synthesized using methodology with reactions global yields ranging from 46%-70%. T. cruzi in vitro effect were evaluated against trypomastigote and amastigote forms and M. tuberculosis activity were towards H37Rv sensitive strain and resistant strains. Discussion: Against T. cruzi, the more active compounds revealed only moderate activity IC50/96h~20 µM for both trypomastigotes and amastigotes intracellular forms. (E)-2-oxo-N'-(3,4,5-trimethoxybenzylidene)-2H-chromene-3-carbohydrazide showed meaningful activity in INH resistant/RIP resistant strain. Conclusion: These compound acting as multitarget could be good leads for the development of new trypanocidal and bactericidal agents.

In Vitro Activities of StrychnosAlkaloids and Extracts against Plasmodium falciparum

1999 ◽  
Vol 43 (9) ◽  
pp. 2328-2331 ◽  
Author(s):  
Michel Frederich ◽  
Marie-Pierre Hayette ◽  
Monique Tits ◽  
Patrick De Mol ◽  
Luc Angenot
Keyword(s):  
Plasmodium Falciparum ◽  
Resistant Strain ◽  
Inhibitory Concentration ◽  
Sensitive Strain ◽  
Resistant Strains

ABSTRACT The in vitro antimalarial activities of 46 alkaloids and extracts from Strychnos species were evaluated. Two types of quasidimeric alkaloids exhibit high and selective activities againstPlasmodium. Strychnopentamine and isostrychnopentamine were active against chloroquine-sensitive and -resistant strains (50% inhibitory concentration [IC50] ≈ 0.15 μM), while dihydrousambarensine exhibited a 30-fold higher activity against the chloroquine-resistant strain (IC50 = 0.03 μM) than it did against the chloroquine-sensitive strain.

scholarly journals Modified Fixed-Ratio Isobologram Method for Studying In Vitro Interactions between Atovaquone and Proguanil or Dihydroartemisinin against Drug-Resistant Strains of Plasmodium falciparum

2004 ◽  
Vol 48 (11) ◽  
pp. 4097-4102 ◽  
Author(s):  
Quinton L. Fivelman ◽  
Ipemida S. Adagu ◽  
David C. Warhurst
Keyword(s):  
Plasmodium Falciparum ◽  
Treatment Failure ◽  
Resistant Strain ◽  
Fixed Ratio ◽  
Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
In Vitro Interactions

ABSTRACT A modified fixed-ratio isobologram method for studying the in vitro interactions between antiplasmodial drugs is described. This method was used to examine the interactions between atovaquone, proguanil, and dihydroartemisinin. The interaction between atovaquone and proguanil was synergistic against atovaquone-sensitive strains K1 and T996; however, there was a loss of synergy against atovaquone-resistant strain NGATV01 isolated after Malarone (the combination of atovaquone and proguanil) treatment failure. While the interaction between atovaquone and dihydroartemisinin was indifferent against isolate NGATV01, the interaction displayed indifference tending toward antagonism against the atovaquone-sensitive strains tested. The relevance of in vitro interactions to in vivo treatment is discussed.

Synthesis and Activity of Some Antimalarial Bisquinolinemethanols

1997 ◽  
Vol 50 (11) ◽  
pp. 1091 ◽  
Author(s):  
Alan F. Cowman, ◽  
Leslie W. Deady, ◽  
Eric Deharo, ◽  
José Desneves ◽  
Leann Tilley
Keyword(s):  
Plasmodium Falciparum ◽  
Resistant Strain ◽  
Cinchona Alkaloids ◽  
Cross Resistance ◽  
Side Chain ◽  
Highly Active ◽  
New Type ◽  
Resistant Strains ◽  
Further Development

A new type of bisquinoline antimalarial, containing the basic side chain of the cinchona alkaloids, has been evaluated. Five bis ethers, from 10,11-dihydrocupreine linked through the 6′-hydroxy group by -(CH2)2n- bridges (n = 2-5) (series A), and six bis amides, from 8′-amino-10,11-dihydrocinchonidine linked by -CO(CH2)2nCO- bridges (n = 1-6) (series B), were synthesized and screened against chloroquine-sensitive and -resistant strains and a mefloquine-resistant strain of Plasmodium falciparum in vitro. Two analogues of series B (n= 4; 5), with a 2-(dibutylamino)-1-hydroxyethyl side chain (series C), were also included. Compounds within series A were generally least active. Among the rest were compounds as active as mefloquine, with diminished cross-resistance to the mefloquine-resistant strain. The most potent (series B, n = 4) was highly active against chloroquine-sensitive, chloroquine-resistant and mefloquine-resistant parasites. Invivo testing, however, showed the compound to be too toxic for further development

scholarly journals Antiplasmodial Activity of Aryltetralone Lignans from Holostylis reniformis

2007 ◽  
Vol 51 (7) ◽  
pp. 2346-2350 ◽  
Author(s):  
Valter F. de Andrade-Neto ◽  
Tito da Silva ◽  
Lucia M. Xavier Lopes ◽  
Virgílio E. do Rosário ◽  
Fernando de Pilla Varotti ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Cell Line ◽  
Plasmodium Berghei ◽  
Resistant Strain ◽  
Lethal Dose ◽  
Hepatic Cell ◽  
Low Toxicity ◽  
Minimum Lethal Dose

ABSTRACT Extracts from Holostylis reniformis were tested in vivo against Plasmodium berghei and in vitro against a chloroquine-resistant strain of Plasmodium falciparum. The hexane extract of the roots was the most active, causing 67% reduction of parasitemia in vivo. From this extract, six lignans, including a new (7′R,8S,8′S)-3′,4′-methylenedioxy-4,5-dimethoxy-2,7′-cyclolignan-7-one, were isolated and tested in vitro against P. falciparum. The three most active lignans showed 50% inhibitor concentrations of ≤0.32 μM. An evaluation of minimum lethal dose (30%) values showed low toxicity for these lignans in a hepatic cell line (Hep G2A16). Therefore, these compounds are potential candidates for the development of antimalarial drugs.

scholarly journals Polygenic and single gene responses to selection for resistance to diazinon in Lucilia cuprina.

Genetics ◽  
1992 ◽  
Vol 130 (3) ◽  
pp. 613-620 ◽  
Author(s):  
J A McKenzie ◽  
A G Parker ◽  
J L Yen
Keyword(s):  
Resistant Strain ◽  
Single Gene ◽  
Natural Populations ◽  
Susceptible Strain ◽  
Selection Line ◽  
Base Population ◽  
Gene Response ◽  
Biochemical Profiles ◽  
Resistant Strains ◽  
Selection For

Abstract Following mutagenesis with ethyl methanesulfonate, selection in a susceptible strain with a concentration of the insecticide diazinon (0.0004%, w/v) above that required to kill 100% of the susceptible strain, the LC100 of that strain, resulted in a single gene response. The resultant four mutant resistant strains have equivalent physiological, genetical and biochemical profiles to a diazinon-resistant strain derived from a natural population and homozygous for the Rop-1 allele. Modification of the microsomal esterase E3 is responsible for resistance in each case. The Rop-1 locus maps approximately 4.4 map units proximal to bu on chromosome IV. Selection within the susceptible distribution, at a concentration of diazinon [0.0001% (w/v)] less than the LC100, resulted in a similar phenotypic response irrespective of whether the base population had been mutagenized. The responses were polygenically based, unique to each selection line and independent of Rop-1. The relevance of the results to selection for insecticide resistance in laboratory and natural populations is discussed.

scholarly journals Diversity-oriented synthesis derived indole based spiro and fused small molecules kills artemisinin-resistant Plasmodium falciparum

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Akshaykumar Nayak ◽  
Himani Saxena ◽  
Chandramohan Bathula ◽  
Tarkeshwar Kumar ◽  
Souvik Bhattacharjee ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Small Molecules ◽  
New Drugs ◽  
Developmental Cycle ◽  
Oxygen Species ◽  
Compound Library ◽  
Diversity Oriented Synthesis ◽  
Resistant Strains ◽  
Acid Catalyzed

Abstract Background Despite numerous efforts to eradicate the disease, malaria continues to remain one of the most dangerous infectious diseases plaguing the world. In the absence of any effective vaccines and with emerging drug resistance in the parasite against the majority of anti-malarial drugs, the search for new drugs is urgently needed for effective malaria treatment. Methods The goal of the present study was to examine the compound library, based on indoles generated through diversity-oriented synthesis belonging to four different architecture, i.e., 1-aryltetrahydro/dihydro-β-carbolines and piperidine/pyrrolidine-fused indole derivatives, for their in vitro anti-plasmodial activity. Trifluoroacetic acid catalyzed transformation involving tryptamine and various aldehydes/ketones provided the library. Results Among all the compounds screened, 1-aryltetrahydro-β-carbolines 2 and 3 displayed significant anti-plasmodial activity against both the artemisinin-sensitive and artemisinin-resistant strain of Plasmodium falciparum. It was observed that these compounds inhibited the overall parasite growth in intra-erythrocytic developmental cycle (IDC) via reactive oxygen species-mediated parasitic death and thus could be potential anti-malarial compounds. Conclusion Overall the compounds 2 and 3 identified in this study shows promising anti-plasmodial activity that can kill both artemisinin-sensitive and artemisinin-resistant strains of P. falciparum.

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

Modern aspects of epidemiology and prevention of typhoid infection (review)

2021 ◽  
pp. 16-26
Author(s):  
Alla Nikolaevna Kaira ◽  
Vyacheslav Fedorovich Lavrov ◽  
Oksana Anatolievna Svitich
Keyword(s):  
Typhoid Fever ◽  
Natural Disasters ◽  
Risk Groups ◽  
Poverty Line ◽  
Epidemiological Surveillance ◽  
Prevention Measures ◽  
Labor Migrants ◽  
Antibiotic Resistant ◽  
The World ◽  
Resistant Strains

Typhoid fever is still an urgent infection, especially in countries where the majority of the population lives below the poverty line, with limited resources, and without the ability to comply with basic hygiene rules. About 11 million cases of typhoid fever are registered worldwide every year, and about 400 people die from this infection every day. The global development of international relations activates migration processes, tourism, and provides rapid movement of significant masses of people around the world, which makes the risk of widespread typhoid infection quite real. In recent years, due to the emergence of antibiotic-resistant strains of S. typhi, treatment of typhoid fever has become less effective. Natural disasters in the form of earthquakes and floods, man-made disasters, as well as military conflicts that occur in different parts of the world, are fertile «soil» for the emergence and spread of typhoid infection, which actualizes the implementation of appropriate prevention measures, including immunoprophylaxis of the disease. Despite the obvious success in the fight against typhoid fever, which consists in a significant reduction in cases of typhoid infection in the world, this dangerous infectious disease still remains an urgent problem, both for health authorities and the population of many countries. Children and young people are still ill, and there is a real risk of infection spreading to any country. Natural disasters pose a real threat of typhoid outbreaks and epidemics. Mass appearance of antibiotic-resistant strains of S. typhi significantly complicates the treatment of patients, dictates the need for constant monitoring of the pathogen’s resistance to antibiotics and the introduction of typhoid immunoprophylaxis for epidemic indications among professional risk groups, labor migrants, and tourists traveling to countries with typhoid-affected countries. There is also a need for reliable epidemiological surveillance of this infection, carried out on an ongoing basis.

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