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Home / Archives for Nogueira F

Nogueira F

N10,N11-di-alkylamine indolo[3,2-b]quinolines as hemozoin inhibitors: design, synthesis and antiplasmodial activity

  • Autores: Coelho L, Egan TJ, Figueiras M, Gut J, Lavrado J, Moreira R, Nogueira F, Paulo A, Rosenthal PJ, Santos SA, Wicht KJ
  • Ano de Publicação: Bioorganic & Medicinal Chemistry
  • Journal: 2015
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/25725608

We recently reported that potent N10,O11-bis-alkylamine indolo[3,2-b]quinoline antimalarials act as hemozoin (Hz) growth inhibitors. To improve access and binding to the target we have now designed novel N10,N11-di-alkylamine bioisosteres.
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Polymorphisms in Plasmodium falciparum K13-propeller in Angola and Mozambique after the introduction of the ACTs

  • Autores: Arez AP, Dias F, Escobar C, Fernandes N, Lobo E, Lobo L, Nogueira F, Pateira S, Teodósio R, Varandas L
  • Ano de Publicação: 2015
  • Journal: PLoS One
  • Link: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0119215

We report the presence of SNPs in Plasmodium falciparum K13-propeller gene in two African countries, Angola and Mozambique, where malaria is a serious public health problem. Samples were collected before and after ACT introduction as first-line treatment. In each country 50 samples collected before and 50 after ACT introduction were analysed.
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Synthesis and antimalarial evaluation of prodrugs of novel fosmidomycin analogues

  • Autores: Barros MT, Faisca Phillips AM, Murtinheira F, Nogueira F
  • Ano de Publicação: 2015
  • Journal: Bioorganic & Medicinal Chemistry Letters
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/25881827

The continuous development of drug resistance by Plasmodium falciparum, the agent responsible for the most severe forms of malaria, creates the need for the development of novel drugs to fight this disease. Fosmidomycin is an effective antimalarial and potent antibiotic, known to act by inhibiting the enzyme 1-deoxy-d-xylulose-5-phosphate reductoisomerase (DXR), essential for the synthesis of isoprenoids in eubacteria and plasmodia, but not in humans.
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Whole-Cell SYBR Green I Assay for Antimalarial Activity Assessment

  • Autores: Lobo E, Machado M, Murtinheira F, Nogueira F
  • Ano de Publicação: 2016
  • Journal: Annals of Clinical and Medical Microbiology
  • Link: https://www.jscimedcentral.com/MedicalMicrobiology/medicalmicrobiology-2-1010.pdf

Malaria parasite growth assessment assays using nucleic acid dye SYBR GreenI are frequently compromised by high background readings due to haemoglobin and detergents in lysis buffer. Here, we have assessed and further validated an intact-cell SYBR Green I-based fluorescence assay (Cell-MSF) for antimalarial activity assessment even of highly fluorescent compounds.
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N-Cinnamoylation of Antimalarial Classics: Effects of Using Acyl Groups Other than Cinnamoyl toward Dual-Stage Antimalarials

  • Autores: Gomes A, Gomes P, Lobo L, Machado M, Nogueira F, Prudencio M, Teixeira C
  • Ano de Publicação: 2015
  • Journal: Chemmedchem
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/26038181

In a follow-up study to our reports of N-cinnamoylated chloroquine and quinacrine analogues as promising dual-stage antimalarial leads with high in vitro potency against both blood-stage Plasmodium falciparum and liver-stage Plasmodium berghei, we decided to investigate the effect of replacing the cinnamoyl moiety with other acyl groups. Thus, a series of N-acylated analogues were synthesized, and their activities against blood- and liver-stage Plasmodium spp. were assessed along with their in vitro cytotoxicities.
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Exploring the 3-piperidin-4-yl-1H-indole scaffold as a novel antimalarial chemotype

  • Autores: Coelho L, Lukens AK, Mazitschek R, Moreira R, Nogueira F, Paulo A, Santos SA, Wirth DF
  • Ano de Publicação: 2015
  • Journal: Journal of Medicinal Chemistry
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/26295174

A series of 3-piperidin-4-yl-1H-indoles with building block diversity was synthesized based on a hit derived from an HTS whole-cell screen against Plasmodium falciparum. Thirty-eight compounds were obtained following a three-step synthetic approach and evaluated for anti-parasitic activity.
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The quinolone-hydroxyquinoline tautomerism in quinolone 3-esters; preserving the 4-oxoquinoline structure to retain antimalarials activity

  • Autores: Coelho L, Cristiano ML, Fausto R, Henriques MS, Horta P, Kuş N, Nogueira F, O'Neill PM, Paixão JA
  • Ano de Publicação: 2015
  • Journal: Journal of Organic Chemistry
  • Link: http://pubs.acs.org/doi/full/10.1021/acs.joc.5b02169

Recent publications report in vitro activity of quinolone 3-esters against the bc1 protein complex of Plasmodium falciparum and the parasite. Docking studies performed in silico at the yeast Qo site established a key role for the 4-oxo and N–H groups in drug-target interactions. Thus, the possibility of 4-oxoquinoline/4-hydroxyquinoline tautomerism may impact in pharmacologic profiles and should be investigated.
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SLC40A1 Q248H allele frequencies and associated SLC40A1 haplotypes in three West African population samples.

  • Autores: Albuquerque D, Alvarez M, Arez AP, Lopes D, Loua KM, Manco L, Millimono TS, Nogueira F, Rath SL, Relvas L, Ribeiro ML, Trovoada Mde J, Varandas L
  • Ano de Publicação: 2011
  • Journal: Annals of human biology
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/?term=SLC40A1+Q248H+allele+frequencies+and+associated+SLC40A1+haplotypes+in+three+West+African+population+samples.

BACKGROUND:
Ferroportin is a transmembrane protein responsible for iron export from enterocytes and macrophages. Mutation c.744G → T (Q248H), located in exon 6 of the ferroportin gene SLC40A1, is found as a polymorphism in populations of African origin. This mutation has been extensively analysed in African-Americans, but poorly studied in native African populations.
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Immunoproteomic analysis of Plasmodium falciparum antigens using sera from patients with clinical history of imported malaria

  • Autores: Costa RM, De Sousa KP, Nogueira F, Silva MS, Vitorino R
  • Ano de Publicação: 2013
  • Journal: Malaria Journal
  • Link: http://www.malariajournal.com/content/12/1/100

Background 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 […]
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In vitro chloroquine resistance for Plasmodium vivax isolates from the Western Brazilian Amazon

  • Autores: Alecrim MG, Brasil LW, Chehuan YF, Costa JS, Costa MR, Lacerda MV, Melo GC, Monteiro WM, Nogueira F, Silveira H
  • Ano de Publicação: 2013
  • Journal: Malaria Journal
  • Link: http://www.malariajournal.com/content/12/1/226

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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