Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 181
Filter
1.
Braz. j. biol ; 83: e247422, 2023. tab, graf
Article in English | MEDLINE, LILACS, VETINDEX | ID: biblio-1285631

ABSTRACT

Abstract Plasmodium falciparum resistance to Chloroquine (CQ) is a significant cause of mortality and morbidity worldwide. There is a paucity of documented data on the prevalence of CQ-resistant mutant haplotypes of Pfcrt and Pfmdr1 genes from malaria-endemic war effected Federally Administered Tribal Areas of Pakistan. The objective of this study was to investigate the prevalence of P. falciparum CQ-resistance in this area. Clinical isolates were collected between May 2017 and May 2018 from North Waziristan and South Waziristan agencies of Federally Administrated Trial Area. Subsequently, Giemsa-stained blood smears were examined to detect Plasmodium falciparum. Extraction of malarial DNA was done from microscopy positive P. falciparum samples, and P. falciparum infections were confirmed by nested PCR (targeting Plasmodium small subunit ribosomal ribonucleic acid (ssrRNA) genes). All PCR confirmed P. falciparum samples were sequenced by pyrosequencing to find out mutation in Pfcrt gene at codon K76T and in pfmdr1 at codons N86Y, Y184F, N1042D, and D1246Y. Out of 121 microscopies positive P. falciparum cases, 109 samples were positive for P. falciparum by nested PCR. Pfcrt K76T mutation was found in 96% of isolates, Pfmdr1 N86Y mutation was observed in 20%, and 11% harboured Y184F mutation. All samples were wild type for Pfmdr1 codon N1042D and D1246Y. In the FATA, Pakistan, the frequency of resistant allele 76T remained high despite the removal of CQ. However, current findings of the study suggest complete fixation of P. falciparum CQ-resistant genotype in the study area.


Resumo A resistência do Plasmodium falciparum à cloroquina (CQ) é uma causa significativa de mortalidade e morbidade em todo o mundo. Há uma escassez de dados documentados sobre a prevalência de haplótipos mutantes CQ-resistentes dos genes Pfcrt e Pfmdr1 da guerra endêmica da malária em áreas tribais administradas pelo governo federal do Paquistão. O objetivo deste estudo foi investigar a prevalência de resistência a CQ de P. falciparum nesta área. Isolados clínicos foram coletados entre maio de 2017 e maio de 2018 nas agências do Waziristão do Norte e do Waziristão do Sul da Área de Ensaio Administrada Federalmente. Posteriormente, esfregaços de sangue corados com Giemsa foram examinados para detectar Plasmodium falciparum. A extração do DNA da malária foi feita a partir de amostras de P. falciparum positivas para microscopia, e as infecções por P. falciparum foram confirmadas por nested PCR (visando genes de ácido ribonucleico ribossômico de subunidade pequena de Plasmodium (ssrRNA)). Todas as amostras de P. falciparum confirmadas por PCR foram sequenciadas por pirosequenciamento para descobrir a mutação no gene Pfcrt no códon K76T e em pfmdr1 nos códons N86Y, Y184F, N1042D e D1246Y. De 121 microscopias de casos positivos de P. falciparum, 109 amostras foram positivas para P. falciparum por nested PCR. A mutação Pfcrt K76T foi encontrada em 96% dos isolados, a mutação Pfmdr1 N86Y foi observada em 20% e 11% abrigou a mutação Y184F. Todas as amostras eram do tipo selvagem para o códon N1042D e D1246Y de Pfmdr1. No FATA, Paquistão, a frequência do alelo resistente 76T permaneceu alta apesar da remoção de CQ. No entanto, as descobertas atuais do estudo sugerem a fixação completa do genótipo resistente a CQ de P. falciparum na área de estudo.


Subject(s)
Plasmodium falciparum/genetics , Antimalarials/pharmacology , Pakistan , Membrane Transport Proteins/genetics , Drug Resistance/genetics , Protozoan Proteins/genetics , Chloroquine/pharmacology , Multidrug Resistance-Associated Proteins/genetics , Alleles
2.
Article in Chinese | WPRIM | ID: wpr-888193

ABSTRACT

As a unicellular organism, Plasmodium displays a panoply of lipid metabolism pathways that are seldom found together in a unicellular organism. These pathways mostly involve the Plasmodium-encoded enzymatic machinery and meet the requirements of membrane synthesis during the rapid cell growth and division throughout the life cycle. Different lipids have varied synthesis and meta-bolism pathways. For example, the major phospholipids are synthesized via CDP-diacylglycerol-dependent pathway in prokaryotes and de novo pathway in eukaryotes, and fatty acids are synthesized mainly via type Ⅱ fatty acid synthesis pathway. The available studies have demonstrated the impacts of artemisinin and its derivatives, the front-line compounds against malaria, on the lipid metabolism of Plasmodium. Therefore, this article reviewed the known lipid metabolism pathways and the effects of artemisinin and its derivatives on these pathways, aiming to deepen the understanding of lipid synthesis and metabolism in Plasmodium and provide a theoretical basis for the research on the mechanisms and drug resistance of artemisinin and other anti-malarial drugs.


Subject(s)
Antimalarials/pharmacology , Artemisinins/therapeutic use , Humans , Lipid Metabolism , Malaria/drug therapy , Plasmodium
3.
Rev. bras. parasitol. vet ; 30(1): e022120, 2021. tab, graf
Article in English | LILACS | ID: biblio-1156221

ABSTRACT

Abstract Neospora caninum is an apicomplexan parasite that causes abortion in cattle, resulting in significant economic losses. There is no commercial treatment for neosporosis, and drug repositioning is a fast strategy to test possible candidates against N. caninum. In this article, we describe the effects of atovaquone, chloroquine, quinine, primaquine and tetracycline on N. caninum proliferation. The IC50 concentrations in N. caninum were compared to the current information based on previous studies for Plasmodium and Toxoplasma gondii, correlating to the described mechanisms of action of each tested drug. The inhibitory patterns indicate similarities and differences among N. caninum, Plasmodium and T. gondii. For example, atovaquone demonstrates high antiparasitic activity in all the analyzed models, while chloroquine does not inhibit N. caninum. On the other hand, tetracycline is effective against Plasmodium and N. caninum, despite its low activity in T. gondii models. The repurposing of antimalarial drugs in N. caninum is a fast and inexpensive way to develop novel formulations using well-established compounds.


Resumo Neospora caninum é um parasita Apicomplexa relacionado a abortos no gado bovino, que resultam em impactos econômicos. Não há tratamento comercial para neosporosis e o reposicionamento de drogas indica uma estratégia rápida para testar candidatos anti-N. caninum. Neste artigo, são descritos os efeitos da atovaquona, cloroquina, quinino, primaquine e tetraciclina na proliferação de N. caninum. As concentrações IC50 em N. caninum foram comparadas com a informação disponível, baseada em estudos publicados previamente para Plasmodium e Toxoplasma gondii, incluindo a correlação com os mecanismos de ação descritos para cada droga testada. Os padrões de inibição indicam pontos de similaridades e diferenças entre N. caninum, Plasmodium e T. gondii. Por exemplo, a atovaquona demonstra uma alta atividade antiparasitária em todos os modelos testados, enquanto a cloroquina não inibe N. caninum. Por outro lado, a tetraciclina é efetiva contra Plasmodium e N. caninum, em contraste com a baixa atividade em modelos de T. gondii. O reposicionamento de drogas antimaláricas em N. caninum é uma forma rápida e de baixo custo para o desenvolvimento de novas formulações que usam compostos bem estabelecidos.


Subject(s)
Neospora/drug effects , Antimalarials/pharmacology , Primaquine/pharmacology , Quinine/pharmacology , Tetracyclines/pharmacology , Chloroquine/pharmacology , Atovaquone/pharmacology
4.
Rev. saúde pública (Online) ; 54: 68, 2020. graf
Article in English | LILACS, BBO | ID: biblio-1127241

ABSTRACT

ABSTRACT Chloroquine (CQ) and its analog hydroxychloroquine (HCQ) were recently included in several clinical trials as potential prophylactic and therapeutic options for SARS-COV-2 infection/covid-19. However, drug effectiveness in preventing, treating, or slowing the progression of the disease is still unknown. Despite some initial promising in vitro results, rigorous pre-clinical animal studies and randomized clinical trials have not been performed yet. On the other hand, while the potential effectiveness of CQ/HCQ is, at best, hypothetical, their side effects are factual and most worrisome, particularly when considering vulnerable groups of patients being treated with these drugs. in this comment, we briefly explain the possible mechanisms of action of CQ/HCQ for treating other diseases, possible actions against covid-19, and their potent side effects, in order to reinforce the necessity of evaluating the benefit-risk balance when widely prescribing these drugs for SARS-COV-2 infection/covid-19. We conclude by strongly recommending against their indiscriminate use.


Subject(s)
Humans , Pneumonia, Viral/drug therapy , Chloroquine/pharmacology , Coronavirus Infections/drug therapy , Betacoronavirus/drug effects , Hydroxychloroquine/pharmacology , Antimalarials/pharmacology , Chloroquine/adverse effects , Chloroquine/pharmacokinetics , Risk Assessment , Pandemics , Contraindications, Drug , SARS-CoV-2 , COVID-19 , Hydroxychloroquine/adverse effects , Hydroxychloroquine/pharmacokinetics , Antimalarials/adverse effects , Antimalarials/pharmacokinetics
5.
Mem. Inst. Oswaldo Cruz ; 113(8): e170452, 2018. tab, graf
Article in English | LILACS | ID: biblio-955116

ABSTRACT

BACKGROUND Malaria is responsible for 429,000 deaths per year worldwide, and more than 200 million cases were reported in 2015. Increasing parasite resistance has imposed restrictions to the currently available antimalarial drugs. Thus, the search for new, effective and safe antimalarial drugs is crucial. Heterocyclic compounds, such as dihydropyrimidinones (DHPM), synthesised via the Biginelli multicomponent reaction, as well as bicyclic compounds synthesised from DHPMs, have emerged as potential antimalarial candidates in the last few years. METHODS Thirty compounds were synthesised employing the Biginelli multicomponent reaction and subsequent one-pot substitution/cyclisation protocol; the compounds were then evaluated in vitro against chloroquine-resistant Plasmodium falciparum parasites (W2 strain). Drug cytotoxicity in baseline kidney African Green Monkey cells (BGM) was also evaluated. The most active in vitro compounds were evaluated against P. berghei parasites in mice. Additionally, we performed an in silico target fishing approach with the most active compounds, aiming to shed some light into the mechanism at a molecular level. RESULTS The synthetic route chosen was effective, leading to products with high purity and yields ranging from 10-84%. Three out of the 30 compounds tested were identified as active against the parasite and presented low toxicity. The in silico study suggested that among all the molecular targets identified by our target fishing approach, Protein Kinase 3 (PK5) and Glycogen Synthase Kinase 3β (GSK-3β) are the most likely molecular targets for the synthesised compounds. CONCLUSIONS We were able to easily obtain a collection of heterocyclic compounds with in vitro anti-P. falciparum activity that can be used as scaffolds for the design and development of new antiplasmodial drugs.


Subject(s)
Drug Design , Parasitic Sensitivity Tests , Antimalarials/chemical synthesis , Antimalarials/pharmacology , Pyrimidinones , Pyrroles
6.
Mem. Inst. Oswaldo Cruz ; 113(10): e180174, 2018. graf
Article in English | LILACS | ID: biblio-1040582

ABSTRACT

Farnesyl diphosphate synthase/geranylgeranyl diphosphate synthase (FPPS/GGPPS) is a key enzyme in the synthesis of isoprenic chains. Risedronate, a bisphosphonate containing nitrogen (N-BP), is a potent inhibitor of blood stage Plasmodium. Here, we show that P. falciparum parasites overexpressing FPPS/GGPPS are more resistant to risedronate, suggesting that this enzyme is an important target, and bisphosphonate analogues can be used as potential antimalarial drugs.


Subject(s)
Animals , Plasmodium falciparum/drug effects , Plasmodium falciparum/enzymology , Farnesyltranstransferase/biosynthesis , Risedronic Acid/pharmacology , Antimalarials/pharmacology , Plasmodium falciparum/growth & development , Reference Values , Drug Resistance , Blotting, Western , Analysis of Variance , Farnesyltranstransferase/analysis , Risedronic Acid/analysis , Antimalarials/analysis
7.
Mem. Inst. Oswaldo Cruz ; 112(10): 692-697, Oct. 2017. tab, graf
Article in English | LILACS | ID: biblio-894841

ABSTRACT

BACKGROUND Endophytic fungi, present mainly in the Ascomycota and Basidiomycota phyla, are associated with different plants and represent important producers of bioactive natural products. Brazil has a rich biodiversity of plant species, including those reported as being endemic. Among the endemic Brazilian plant species, Vellozia gigantea (Velloziaceae) is threatened by extinction and is a promising target to recover endophytic fungi. OBJECTIVE The present study focused on bioprospecting of bioactive compounds of the endophytic fungi associated with V. gigantea, an endemic, ancient, and endangered plant species that occurs only in the rupestrian grasslands of Brazil. METHODS The capability of 285 fungal isolates to produce antimicrobial and antimalarial activities was examined. Fungi were grown at solid-state fermentation to recover their crude extracts in dichloromethane. Bioactive extracts were analysed by chromatographic fractionation and NMR and displayed compounds with antimicrobial, antimycobacterial, and antimalarial activities. FINDINGS Five fungi produced antimicrobial and antimalarial compounds. Extracts of Diaporthe miriciae showed antifungal, antibacterial, and antimalarial activities; Trichoderma effusum displayed selective antibacterial activity against methicillin-resistant Staphylococcus aureus and Mycobacterium intracellulare; and three Penicillium species showed antibacterial activity. D. miriciae extract contained highly functionalised secondary metabolites, yielding the compound epoxycytochalasin H with high antimalarial activity against the chloroquine-resistant strain of Plasmodium falciparum, with an IC50 approximately 3.5-fold lower than that with chloroquine. MAIN CONCLUSION Our results indicate that V. gigantea may represent a microhabitat repository hotspot of potential fungi producers of bioactive compounds and suggest that endophytic fungal communities might be an important biological component contributing to the fitness of the plants living in the rupestrian grassland.


Subject(s)
Plasmodium/drug effects , Microbial Sensitivity Tests , Magnoliopsida/classification , Magnoliopsida/microbiology , Mitosporic Fungi/drug effects , Gram-Negative Aerobic Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacology , Antifungal Agents/isolation & purification , Antifungal Agents/pharmacology , Antimalarials/isolation & purification , Antimalarials/pharmacology , Tropical Climate , Biological Assay , Candida/drug effects , Endophytes/chemistry
8.
Mem. Inst. Oswaldo Cruz ; 112(4): 299-308, Apr. 2017. tab, graf
Article in English | LILACS | ID: biblio-841780

ABSTRACT

BACKGROUND Malaria persists as a major public health problem. Atovaquone is a drug that inhibits the respiratory chain of Plasmodium falciparum, but with serious limitations like known resistance, low bioavailability and high plasma protein binding. OBJECTIVES The aim of this work was to perform molecular modelling studies of 2-hydroxy-1,4-naphthoquinones analogues of atovaquone on the Qo site of P. falciparum cytochrome bc1 complex (Pfbc1) to suggest structural modifications that could improve their antimalarial activity. METHODS We have built the homology model of the cytochrome b (CYB) and Rieske iron-sulfur protein (ISP) subunits from Pfbc1 and performed the molecular docking of 41 2-hydroxy-1,4-naphthoquinones with known in vitro antimalarial activity and predicted to act on this target. FINDINGS Results suggest that large hydrophobic R2 substituents may be important for filling the deep hydrophobic Qo site pocket. Moreover, our analysis indicates that the H-donor 2-hydroxyl group may not be crucial for efficient binding and inhibition of Pfbc1 by these atovaquone analogues. The C1 carbonyl group (H-acceptor) is more frequently involved in the important hydrogen bonding interaction with His152 of the Rieske ISP subunit. MAIN CONCLUSIONS Additional interactions involving residues such as Ile258 and residues required for efficient catalysis (e.g., Glu261) could be explored in drug design to avoid development of drug resistance by the parasite.


Subject(s)
Plasmodium falciparum/drug effects , Electron Transport Complex III/chemistry , Antimalarials/pharmacology , Antimalarials/chemistry , Naphthoquinones/chemistry , Sequence Analysis, Protein
9.
Rev. Soc. Bras. Med. Trop ; 49(5): 586-592, Sept.-Oct. 2016. tab, graf
Article in English | LILACS | ID: lil-798117

ABSTRACT

Abstract INTRODUCTION: Malaria and leishmaniasis are prevalent in tropical regions, which have environmental characteristics that are highly favorable to protozoa and vectors of these diseases; the transmission of these infections in sub-tropical regions, although recognized, represents only a small fraction of cases. Plants are constantly being used in the search for and acquisition of new drugs, and many compounds derived from them have been used to combat various diseases. In this study, we evaluated the action of the dichloromethanolic extract of Myrciaria dubia leaves against the protozoa Plasmodium falciparum, Leishmania amazonensis, Leishmania braziliensis, and Leishmania chagasi through bioassays. METHODS The extract from M. dubia was tested for its anti-P. falciparum activity in an anti-histidine-rich protein II immunosorbent assay. The antileishmanial assays were performed using the resazurin method, while cytotoxicity against human hepatoma (HepG2) strain was determined using the colorimetric MTT [3-(4, 5-dimethyl-2- thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide] method. RESULTS The M. dubia extract presented a half-maximal inhibitory concentration equal to 2.35 (1.05)μg/mL for P. falciparum, 190.73 (6.41) μg/mL for L. amazonensis, and greater than equal to 200µg/mL for L. chagasi and L. braziliensis strains. The cytotoxic concentration for 50% of the cells was above 500μg/mL for HepG2, indicating no toxicity and greater selectivity against parasites. CONCLUSIONS The results obtained indicate the presence of antiplasmodial and leishmanicidal bioactive compounds in the dichloromethanolic extracts of M. dubia leaves, and point towards future studies to elucidate the mechanism of action for each physiological effect.


Subject(s)
Humans , Plasmodium falciparum/drug effects , Plant Extracts/pharmacology , Myrtaceae/chemistry , Leishmania/drug effects , Antimalarials/pharmacology , Antiprotozoal Agents/pharmacology , Plant Extracts/toxicity , Immunoenzyme Techniques , Colorimetry , Inhibitory Concentration 50 , Parasitic Sensitivity Tests , Hep G2 Cells/drug effects , Leishmania/classification , Antimalarials/isolation & purification , Antimalarials/toxicity , Antiprotozoal Agents/isolation & purification , Antiprotozoal Agents/toxicity
10.
Mem. Inst. Oswaldo Cruz ; 111(7): 450-453, tab
Article in English | LILACS | ID: lil-787558

ABSTRACT

Ever increasing multi-drug resistance by Plasmodium falciparum is creating new challenges in malaria chemotherapy. In the absence of licensed vaccines, treatment and prevention of malaria is heavily dependent on drugs. Potency, range of activity, safety, low cost and ease of administration are crucial issues in the design and formulation of antimalarials. We have tested three synthetic ozonides NAC89, LC50 and LCD67 in vitro and in vivo against multidrug resistant Plasmodium. In vitro, LC50 was at least 10 times more efficient inhibiting P. falciparum multidrug resistant Dd2 strain than chloroquine and mefloquine and as efficient as artemisinin (ART), artesunate and dihydroartemisinin. All three ozonides showed high efficacy in clearing parasitaemia in mice, caused by multi-drug resistant Plasmodium chabaudi strains, by subcutaneous administration, demonstrating high efficacy in vivo against ART and artesunate resistant parasites.


Subject(s)
Humans , Animals , Female , Antimalarials/pharmacology , Malaria, Falciparum/parasitology , Plasmodium falciparum/drug effects , Artemisinins/pharmacology , Chloroquine/pharmacology , Disease Models, Animal , Mefloquine/pharmacology , Mice , Parasitemia/drug therapy
11.
Article in English | LILACS | ID: lil-758425

ABSTRACT

The preoccupation to find new drugs for the treatment of malaria is increasing steadily due to the resistance of the parasite, which is a threat to disease control, The present study describes a literature review on the antimalarial ethnopharmacology (Anti-Plasmodium falciparum - in vitro) of the Brazilian Amazon plants, It was found a great diversity of plant species in the Brazilian Amazon with potential for research of new herbal and secondary metabolites with antiplasmodial action, in addition to treating other neglected parasitic diseases, However, for these studies is needed in addition to financial support, the interaction between different laboratories and research groups for the formation of multidisciplinary and interdisciplinary teams, which will enhance the research level in the region and increase the likelihood of new antimalarial drugs discovery...


Está cada vez maior a necessidade em se buscar novos fármacos para o tratamento da malária, principalmente devido à resistência do parasito, o que é uma ameaça ao controle da doença. O presente estudo descreve uma revisão bibliográfica sobre a etnofarmacologia antimalárica (Anti-Plasmodium falciparum - in vitro) de plantas da Amazônia brasileira. Constatou-se uma grande diversidade de espécies vegetais na Amazônia brasileira com potencial para a investigação de novos fitoterápicos e metabólitos secundários com ação antiplasmodial, além do tratamento de outras parasitoses negligenciadas. Porém, para a realização desses estudos são necessários além de apoio financeiro, a interação entre diferentes laboratórios e grupos de pesquisa para a formação de equipes multidisciplinares e interdisciplinares, o que irá potencializar o nível da pesquisa na região e aumentar a probabilidade de descoberta de novos fármacos antimaláricos...


Subject(s)
Humans , Antimalarials/pharmacology , Ethnopharmacology/trends , Malaria, Falciparum/drug therapy , Brazil , Drug Resistance
12.
Mem. Inst. Oswaldo Cruz ; 110(8): 981-988, Dec. 2015. tab, graf
Article in English | LILACS | ID: lil-769827

ABSTRACT

This work reports the in vitro activity against Plasmodium falciparumblood forms (W2 clone, chloroquine-resistant) of tamoxifen-based compounds and their ferrocenyl (ferrocifens) and ruthenocenyl (ruthenocifens) derivatives, as well as their cytotoxicity against HepG2 human hepatoma cells. Surprisingly with these series, results indicate that the biological activity of ruthenocifens is better than that of ferrocifens and other tamoxifen-like compounds. The synthesis of a new metal-based compound is also described. It was shown, for the first time, that ruthenocifens are good antiplasmodial prototypes. Further studies will be conducted aiming at a better understanding of their mechanism of action and at obtaining new compounds with better therapeutic profile.


Subject(s)
Animals , Humans , Antimalarials/pharmacology , Coordination Complexes/chemical synthesis , Ferrous Compounds/pharmacology , Organometallic Compounds/pharmacology , Plasmodium falciparum/drug effects , Ruthenium/pharmacology , Antimalarials/chemical synthesis , Cell Line , Chromatography, Thin Layer , Coordination Complexes/pharmacology , Cytotoxins/pharmacology , Ferrous Compounds/chemical synthesis , Haplorhini , /parasitology , In Vitro Techniques , Organometallic Compounds/chemical synthesis , Ruthenium/chemistry , Tamoxifen/chemistry
13.
Mem. Inst. Oswaldo Cruz ; 110(7): 906-913, Nov. 2015. tab, graf
Article in English | LILACS | ID: lil-764592

ABSTRACT

Several species of Aspidospermaplants are used to treat diseases in the tropics, including Aspidosperma ramiflorum, which acts against leishmaniasis, an activity that is experimentally confirmed. The species, known as guatambu-yellow, yellowperoba, coffee-peroba andmatiambu, grows in the Atlantic Forest of Brazil in the South to the Southeast regions. Through a guided biofractionation of A. ramiflorumextracts, the plant activity against Plasmodium falciparumwas evaluated in vitro for toxicity towards human hepatoma G2 cells, normal monkey kidney cells and nonimmortalised human monocytes isolated from peripheral blood. Six of the seven extracts tested were active at low doses (half-maximal drug inhibitory concentration < 3.8 µg/mL); the aqueous extract was inactive. Overall, the plant extracts and the purified compounds displayed low toxicity in vitro. A nonsoluble extract fraction and one purified alkaloid isositsirikine (compound 5) displayed high selectivity indexes (SI) (= 56 and 113, respectively), whereas compounds 2 and 3 were toxic (SI < 10). The structure, activity and low toxicity of isositsirikine in vitro are described here for the first time in A. ramiflorum, but only the neutral and precipitate plant fractions were tested for activity, which caused up to 53% parasitaemia inhibition of Plasmodium bergheiin mice with blood-induced malaria. This plant species is likely to be useful in the further development of an antimalarial drug, but its pharmacological evaluation is still required.


Subject(s)
Animals , Humans , Mice , Antimalarials/pharmacology , Aspidosperma/chemistry , Plant Extracts/pharmacology , Plasmodium berghei/drug effects , Plasmodium falciparum/drug effects , Antimalarials/isolation & purification , Antimalarials/toxicity , Cell Line , Dose-Response Relationship, Drug , Parasitic Sensitivity Tests
14.
Rev. paul. pediatr ; 33(1): 19-27, Jan-Mar/2015. tab, graf
Article in English | LILACS | ID: lil-744705

ABSTRACT

OBJECTIVE: To analyze the neonatal screening program for hemoglobinopathies in São Carlos, Southeast Brazil, by investigating a series of cases in which the screening test was abnormal. More specifically, it was aimed to know the information regarding the neonatal screening received by mothers at the hospital and at primary health care, in addition to information related to genetic counseling. METHODS: A descriptive study that enrolled 119 mothers, accounting for 73% of all children born between 2010 and 2011 with abnormal results of neonatal screening for hemoglobinopathies. The mothers completed a questionnaire that assessed the information received at hospital and primary health care, and issues related to genetic counseling. Descriptive statistics was performed. RESULTS: Of the 119 participating mothers, 69 (58%) had children with sickle cell trait, 22 (18.5%) with hemoglobin C trait, 18 (15.1%) with alpha thalassemia trait and, in 10 cases (8.4%), the result was inconclusive. At the hospital, 118 mothers (99.2%) received information about where to go to collect the test and 115 (96.6%) were informed about the correct time to collect the test. Only 4 mothers (3.4%) were informed about which diseases are investigated and the risks of not performing the screening. Seventeen mothers (14.3%) recognized the difference between trait and disease, and 42 (35.3%) considered that a positive screening test could have implications for future pregnancies. In 70 cases (58.8%), the child's physician was not informed about the screening test results. CONCLUSIONS: The neonatal screening program needs further improvement. In both scenarios investigated, health professionals demonstrated a lack of training in providing information to mothers and families. .


OBJETIVO: Fazer uma análise do programa de triagem neonatal de hemoglobinopatias no município de São Carlos, São Paulo, Brasil, por meio da investigação de série de casos cujo resultado do teste de rastreio foi alterado. Objetivou-se conhecer as informações a respeito da triagem neonatal recebidas pelas mães na maternidade e na atenção primária à saúde, além das informações relacionadas à orientação genética. MÉTODOS: Estudo descritivo, no qual participaram 119 mães cujos filhos apresentaram teste de triagem de hemoglobinopatia alterado, o que correspondeu a 73% das crianças nascidas entre 2010 e 2011 com resultado de triagem neonatal para hemoglobinopatia anormal. As mães responderam um questionário que avaliou informações recebidas na maternidade e na atenção primária à saúde, além de aspectos relacionados à orientação genética. Foi feita estatística descritiva dos dados. RESULTADOS: Das 119 mães participantes, 69 (58%) tinham filhos com traço falciforme, 22 (18,5%) traço C, 18 (15,1%) traço alfatalassêmico e 10 (8,4%) resultado inconclusivo. Na maternidade, 118 mães (99,2%) receberam informação sobre onde ir e 115 (96,6%) foram orientadas sobre o momento correto para coleta do teste. Somente quatro mães (3,4%) foram informadas sobre quais doenças seriam investigadas e os riscos de não fazer o rastreio. Das 119 mães participantes, 17 (14,3%) reconheceram a diferença entre traço e doença e 42 (35,3%) consideraram que um teste alterado poderia ter implicações para futuras gestações. Em 70 casos (58,8%), o médico da criança não foi informado sobre o resultado da triagem. CONCLUSÕES: O programa de triagem neonatal necessita de aperfeiçoamento. Nos dois cenários investigados, os profissionais de saúde carecem de treinamento para orientar mães e famílias. .


Subject(s)
Antimalarials/pharmacology , Oxazines/pharmacology , Plasmodium falciparum/drug effects , Pyridines/pharmacology , Antimalarials/chemical synthesis , Antimalarials/metabolism , Dose-Response Relationship, Drug , Microbial Sensitivity Tests , Molecular Structure , Oxazines/chemical synthesis , Oxazines/metabolism , Parasitic Sensitivity Tests , Pyridines/chemical synthesis , Pyridines/metabolism , Structure-Activity Relationship
15.
Article in English | WPRIM | ID: wpr-130572

ABSTRACT

Pyronaridine and artesunate have been shown to be effective in falciparum malaria treatment. However, pyronaridine is rarely used in Hainan Island clinically, and artesunate is not widely used as a therapeutic agent. Instead, conventional antimalarial drugs, chloroquine and piperaquine, are used, explaining the emergence of chloroquine-resistant Plasmodium falciparum. In this article, we investigated the sensitivity of P. falciparum to antimalarial drugs used in Hainan Island for rational drug therapy. We performed in vivo (28 days) and in vitro tests to determine the sensitivity of P. falciparum to antimalarial drugs. Total 46 patients with falciparum malaria were treated with dihydroartemisinin/piperaquine phosphate (DUO-COTECXIN) and followed up for 28 day. The cure rate was 97.8%. The mean fever clearance time (22.5+/-10.6 hr) and the mean parasite clearance time (27.3+/-12.2 hr) showed no statistical significance with different genders, ages, temperatures, or parasite density (P>0.05). The resistance rates of chloroquine, piperaquine, pyronarididine, and artesunate detected in vitro were 71.9%, 40.6%, 12.5%, and 0%, respectively (Ppiperaquine>pyronarididine>artesunate. The inhibitory dose 50 (IC50) was 3.77x10(-6) mol/L, 2.09x10(-6) mol/L, 0.09x10(-6) mol/L, and 0.05x10(-6) mol/L, and the mean concentrations for complete inhibition (CIMC) of schizont formation were 5.60x10(-6) mol/L, 9.26x10(-6) mol/L, 0.55x10(-6) mol/L, and 0.07x10(-6) mol/L, respectively. Dihydroartemisinin showed a strong therapeutic effect against falciparum malaria with a low toxicity.


Subject(s)
Adolescent , Adult , Aged , Antimalarials/pharmacology , Child , Child, Preschool , China , Female , Humans , Inhibitory Concentration 50 , Malaria, Falciparum/drug therapy , Male , Middle Aged , Parasitic Sensitivity Tests , Plasmodium falciparum/drug effects , Treatment Outcome , Young Adult
16.
Article in English | WPRIM | ID: wpr-130570

ABSTRACT

The aim of the study was to explore the possible molecular markers of chloroquine resistance in Plasmodium vivax isolates in Thailand. A total of 30 P. vivax isolates were collected from a malaria endemic area along the Thai-Myanmar border in Mae Sot district of Thailand. Dried blood spot samples were collected for analysis of Pvmdr1 and Pvcrt-o polymorphisms. Blood samples (100 mul) were collected by finger-prick for in vitro chloroquine susceptibility testing by schizont maturation inhibition assay. Based on the cut-off IC50 of 100 nM, 19 (63.3%) isolates were classified as chloroquine resistant P. vivax isolates. Seven non-synonymous mutations and 2 synonymous were identified in Pvmdr1 gene. Y976F and F1076L mutations were detected in 7 (23.3%) and 16 isolates (53.3%), respectively. Analysis of Pvcrt-o gene revealed that all isolates were wild-type. Our results suggest that chloroquine resistance gene is now spreading in this area. Monitoring of chloroquine resistant molecular markers provide a useful tool for future control of P. vivax malaria.


Subject(s)
Amino Acid Substitution , Antimalarials/pharmacology , Chloroquine/pharmacology , Drug Resistance , Humans , Inhibitory Concentration 50 , Malaria, Vivax/parasitology , Membrane Transport Proteins/genetics , Multidrug Resistance-Associated Proteins/genetics , Mutation, Missense , Myanmar , Parasitic Sensitivity Tests , Plasmodium vivax/drug effects , Protozoan Proteins/genetics , Thailand
17.
Article in English | WPRIM | ID: wpr-130565

ABSTRACT

Pyronaridine and artesunate have been shown to be effective in falciparum malaria treatment. However, pyronaridine is rarely used in Hainan Island clinically, and artesunate is not widely used as a therapeutic agent. Instead, conventional antimalarial drugs, chloroquine and piperaquine, are used, explaining the emergence of chloroquine-resistant Plasmodium falciparum. In this article, we investigated the sensitivity of P. falciparum to antimalarial drugs used in Hainan Island for rational drug therapy. We performed in vivo (28 days) and in vitro tests to determine the sensitivity of P. falciparum to antimalarial drugs. Total 46 patients with falciparum malaria were treated with dihydroartemisinin/piperaquine phosphate (DUO-COTECXIN) and followed up for 28 day. The cure rate was 97.8%. The mean fever clearance time (22.5+/-10.6 hr) and the mean parasite clearance time (27.3+/-12.2 hr) showed no statistical significance with different genders, ages, temperatures, or parasite density (P>0.05). The resistance rates of chloroquine, piperaquine, pyronarididine, and artesunate detected in vitro were 71.9%, 40.6%, 12.5%, and 0%, respectively (Ppiperaquine>pyronarididine>artesunate. The inhibitory dose 50 (IC50) was 3.77x10(-6) mol/L, 2.09x10(-6) mol/L, 0.09x10(-6) mol/L, and 0.05x10(-6) mol/L, and the mean concentrations for complete inhibition (CIMC) of schizont formation were 5.60x10(-6) mol/L, 9.26x10(-6) mol/L, 0.55x10(-6) mol/L, and 0.07x10(-6) mol/L, respectively. Dihydroartemisinin showed a strong therapeutic effect against falciparum malaria with a low toxicity.


Subject(s)
Adolescent , Adult , Aged , Antimalarials/pharmacology , Child , Child, Preschool , China , Female , Humans , Inhibitory Concentration 50 , Malaria, Falciparum/drug therapy , Male , Middle Aged , Parasitic Sensitivity Tests , Plasmodium falciparum/drug effects , Treatment Outcome , Young Adult
18.
Article in English | WPRIM | ID: wpr-130563

ABSTRACT

The aim of the study was to explore the possible molecular markers of chloroquine resistance in Plasmodium vivax isolates in Thailand. A total of 30 P. vivax isolates were collected from a malaria endemic area along the Thai-Myanmar border in Mae Sot district of Thailand. Dried blood spot samples were collected for analysis of Pvmdr1 and Pvcrt-o polymorphisms. Blood samples (100 mul) were collected by finger-prick for in vitro chloroquine susceptibility testing by schizont maturation inhibition assay. Based on the cut-off IC50 of 100 nM, 19 (63.3%) isolates were classified as chloroquine resistant P. vivax isolates. Seven non-synonymous mutations and 2 synonymous were identified in Pvmdr1 gene. Y976F and F1076L mutations were detected in 7 (23.3%) and 16 isolates (53.3%), respectively. Analysis of Pvcrt-o gene revealed that all isolates were wild-type. Our results suggest that chloroquine resistance gene is now spreading in this area. Monitoring of chloroquine resistant molecular markers provide a useful tool for future control of P. vivax malaria.


Subject(s)
Amino Acid Substitution , Antimalarials/pharmacology , Chloroquine/pharmacology , Drug Resistance , Humans , Inhibitory Concentration 50 , Malaria, Vivax/parasitology , Membrane Transport Proteins/genetics , Multidrug Resistance-Associated Proteins/genetics , Mutation, Missense , Myanmar , Parasitic Sensitivity Tests , Plasmodium vivax/drug effects , Protozoan Proteins/genetics , Thailand
19.
Article in English | WPRIM | ID: wpr-225155

ABSTRACT

The parasite Plasmodium falciparum causes severe malaria and is the most dangerous to humans. However, it exhibits resistance to their drugs. Farnesyltransferase has been identified in pathogenic protozoa of the genera Plasmodium and the target of farnesyltransferase includes Ras family. Therefore, the inhibition of farnesyltransferase has been suggested as a new strategy for the treatment of malaria. However, the exact functional mechanism of this agent is still unknown. In addition, the effect of farnesyltransferase inhibitor (FTIs) on mitochondrial level of malaria parasites is not fully understood. In this study, therefore, the effect of a FTI R115777 on the function of mitochondria of P. falciparum was investigated experimentally. As a result, FTI R115777 was found to suppress the infection rate of malaria parasites under in vitro condition. It also reduces the copy number of mtDNA-encoded cytochrome c oxidase III. In addition, the mitochondrial membrane potential (DeltaPsim) and the green fluorescence intensity of MitoTracker were decreased by FTI R115777. Chloroquine and atovaquone were measured by the mtDNA copy number as mitochondrial non-specific or specific inhibitor, respectively. Chloroquine did not affect the copy number of mtDNA-encoded cytochrome c oxidase III, while atovaquone induced to change the mtDNA copy number. These results suggest that FTI R115777 has strong influence on the mitochondrial function of P. falciparum. It may have therapeutic potential for malaria by targeting the mitochondria of parasites.


Subject(s)
Antimalarials/pharmacology , Enzyme Inhibitors/pharmacology , Farnesyltranstransferase/antagonists & inhibitors , Humans , Malaria, Falciparum/drug therapy , Mitochondria/drug effects , Plasmodium falciparum/drug effects , Protozoan Proteins/antagonists & inhibitors , Quinolones/pharmacology
20.
European J Med Plants ; 2014 Dec; 4(12): 1378-1387
Article in English | IMSEAR | ID: sea-164204

ABSTRACT

Aim: Antiplasmodial potential of traditional medicinal plant Thlaspi arvense against Plasmodium falciparum in vitro has been evaluated. Cytotoxicity of plant extract against HeLa cell lines and normal fibroblasts has also been observed. Place and Duration of the Study: Department of Zoology, Panjab University, Chandigarh, India, between May 2013 to April 2014. Materials and Methods: Ethanolic whole plant extract of Thlaspi arvense (EWETA) was analyzed for its phytochemical constituents. In vitro cytotoxicity was determined colorimetrically by MTT assay. WHO protocol, based on assessment of schizont maturation inhibition, was employed for the evaluation of in vitro antiplasmodial activity of plant extract. Results: Phytochemical screening of EWETA revealed the presence of diterpenes, triterpenes, steroids, anthraquinones and phytosterols. EWETA was observed to inhibit schizont maturation of both chloroquine-sensitive (MRC-2) and resistant (RKL-9) strains of P. falciparum with IC50<5μg/ml and =5μg/ml respectively. The extract was revealed to be safe against both HeLa cells and normal fibroblasts with CC50>1000μg/ml. Selectivity index for Thlaspi arvense was calculated to be >200 and =200 both for chloroquine sensitive and chloroquine-resistant strains of P. falciparum with both HeLa and normal fibroblasts. Conclusion: Plant extract possesses considerable in vitro antimalarial activity with high selectivity index (SI>10) pointing field pennycress to be an active antimalarial. Hence, present study provides scientific evidence for traditional usage of the plant as an antipyretic agent.


Subject(s)
Antimalarials/pharmacology , Humans , India , Malaria, Falciparum/drug therapy , Medicine, Traditional , Microbial Sensitivity Tests , Microbial Viability/drug effects , Phytotherapy , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Extracts/toxicity , Plasmodium falciparum/drug effects , Thlaspi
SELECTION OF CITATIONS
SEARCH DETAIL