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Nogueira F

Early transcriptional response to chloroquine of the Plasmodium falciparum antioxidant defence in sensitive and resistant strains

Resistance to chloroquine (CQ) in Plasmodium falciparum has a major impact on malaria control worldwide. To gain insight into early parasite stress response, mRNA expression profiles were determined for a set of 10 antioxidant defence genes in synchronized CQ-sensitive (3D7) and CQ-resistant (Dd2) clones under transient IC50 CQ-exposure (Dd2, 200 nM; 3D7, 14 nM). Upon 2-h CQ challenge, the mRNA upregulation detected was greater in 3D7 (six genes overexpressed at 1/3 of the intraerythrocytic cycle) than in Dd2 clone (three genes responding), providing evidence of an early transcriptional response to CQ-induced oxidative stress which might underlie some of the parasite’s metabolic adaptation to the drug.
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Immunoproteomic analysis of Plasmodium falciparum antigens using sera from patients with clinical history of imported malaria

The malaria caused by Plasmodium falciparum remains a serious public health problem in the world, due largely to the absence of an effective vaccine. There is a lack of information on the structural properties and antigens capable of activating the immunological mechanisms for the induction of protective immunity. Therefore, the objective of this study is to evaluate the serological reactivity of sera from individuals with imported malaria and identify major immunogenic proteins.
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. In vitro chloroquine resistance for Plasmodium vivax isolates from the Western Brazilian Amazon

Chloroquine (CQ) and primaquine (PQ) are still the drugs of choice to treat Plasmodium vivax malaria in many endemic areas, Brazil included. There is in vivo evidence for the P. vivax resistance to CQ in the Brazilian Amazon, where the increase in the proportion of P. vivax malaria parallels the increase of unusual clinical complications related to this species. In this study, in vitro CQ and mefloquine (MQ)-susceptibility of P. vivax isolates from the Western Brazilian Amazon was tested using the double-site enzyme-linked lactate dehydrogenase immunodetection (DELI) assay.
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Plasmodium vivax chloroquine resistance and anemia in the western Brazilian Amazon

In Latin America, data on chloroquine (CQ)-resistant Plasmodium vivax is limited, even with the current research efforts to sustain an efficient malaria control program in all these endemic countries, where malaria still is a major public health issue.
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Novel endoperoxide-based transmission-blocking antimalarials with liver- and blood-schizontocidal activities

In a search for effective compounds against both the blood- and liver-stages of infection by malaria parasites with the ability to block the transmission of the disease to mosquito vectors, a series of hybrid compounds combining either a 1,2,4-trioxane or 1,2,4,5-tetraoxane and 8-aminoquinoline moieties were synthesized and screened for their antimalarial activity.
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Methods for assessment of antimalarial activity in the different phases of the Plasmodium life cycle

Malaria is a mosquito-borne disease caused by parasites of the genus Plasmodium. In humans, parasites multiply in the liver and then infect red blood cells. The Plasmodium life cycle consists of a sexual phase in the mosquito vector (sporogony) and an asexual phase in the vertebrate host (schizogony); both life cycle phases can be detected in assays.
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N-cinnamoylation of antimalarial classics: quinacrine analogues with decreased toxicity and dual-stage activity

Plasmodium falciparum, the causative agent of the most lethal form of malaria, is becoming increasingly resistant to most available drugs. A convenient approach to combat parasite resistance is the development of analogues of classical antimalarial agents, appropriately modified in order to restore their relevance in antimalarial chemotherapy.
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Bis-alkylamineIndolo[3,2-b]quinolines as hemozoin ligands: implications for antimalarialcytostatic and cytocidal activities

To get insight into the relevance of targeting hemozoin (Hz) crystals, two isomeric series, N5,N10-bis-alkylamine (2a-k) and N10,O11-bis-alkylamine (3a-k) indolo[3,2-b]quinolines, were evaluated for their in vitro activity against chloroquine (CQ)-resistant and sensitive strains of Plasmodium falciparum.
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Probing the aurone scaffold against Plasmodium falciparum: design, synthesis and antimalarial activity

A library comprising 44 diversely substituted aurones derivatives was synthesized by straightforward aldol condensation reactions of benzofuranones and the appropriately substituted benzaldehydes. Microwave enhanced synthesis using palladium catalyzed protocols was introduced as a powerful strategy for extending the chemical space around the aurone scaffold.
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Prevalence of pfmdr1 alleles associated with artemether-lumefantrine tolerance/resistance in Maputo before and after the implementation of artemisinin-based combination therapy

Mozambique implemented artemisinin-based combinations therapy (ACT) using artemether-lumefantrine (AL) as the first-line treatment for uncomplicated malaria in 2009. AL remains highly efficacious, but widespread use may soon facilitate emergence of artemisinin tolerance/resistance. The prevalence of pfmdr1 different alleles in Maputo and Mozambique is not known, either after or before the introduction of ACT. Pfmdr1 molecular markers related to Plasmodium falciparum susceptibility were analysed before and after transition to ACT.
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