Anderson Assunção Andrade

Publications (2)7.36 Total impact

• Article: Synthesis, antimalarial activity, and intracellular targets of MEFAS, a new hybrid compound derived from mefloquine and artesunate.

  Fernando de Pilla Varotti, Ana Cristina C Botelho, Anderson Assunção Andrade, Renata C de Paula, Elaine M S Fagundes, Alessandra Valverde, Lúcia M U Mayer, Jorge Souza Mendonça, Marcus V N de Souza, Núbia Boechat, Antoniana Ursine Krettli
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  ABSTRACT: A new synthetic antimalarial drug, a salt derived from two antimalarial molecules, mefloquine (MQ) and artesunate (AS), here named MEFAS, has been tested for its pharmacological activity. Combinations of AS plus MQ hydrochloride are currently being used in areas with drug-resistant Plasmodium falciparum parasites; although AS clears parasitemia in shorter time periods than any other antimalarial drug, it does not cure infected patients; in addition, MQ causes side effects and is rather expensive, important problems considering that malaria affects mostly populations in poor countries. Here, we show that MEFAS is more effective than the combination of AS and MQ, tested in parallel at different mass proportions, against P. falciparum (chloroquine-resistant clone W2 and chloroquine-sensitive clone 3D7) in vitro and in mice infected with Plasmodium berghei, promoting cure of this infection. MEFAS tested against HepG2 hepatoma cells exhibited lower toxicity than the antimalarials AS and MQ alone or combined. Possible targets of MEFAS have been studied by confocal microscopy using fluorescent probes (Fluo-4 AM and BCECF-AM) in P. falciparum synchronous culture of W2-infected red blood cells. Dynamic images show that MEFAS exhibited intracellular action increasing cytoplasmic Ca(2+) at 1.0 ng/ml. This effect was also observed in the presence of tapsigargin, an inhibitor of SERCA, suggesting an intracellular target distinct from the endoplasmic reticulum. Trophozoites loaded with BCECF-AM, when treated with MEFAS, were still able to mobilize protons from the digestive vacuole (DV), altering the pH gradient. However, in the presence of bafilomycin A1, an inhibitor of the H(+) pump from acidic compartments of eukaryotic cells, MEFAS had no action on the DV. In conclusion, the endoplasmic reticulum and DV are intracellular targets for MEFAS in Plasmodium sp., suggesting two modes of action of this new salt. Our data support MEFAS as a candidate for treating human malaria.
  Antimicrobial Agents and Chemotherapy 09/2008; 52(11):3868-74. · 4.84 Impact Factor
• Article: Enhanced activity of mefloquine and artesunic acid against Plasmodium falciparum in vitro and P. berghei in mice by combination with ciprofloxacin.

  Anderson Assunção Andrade, Fernando de Pilla Varotti, Isabela Oliveira de Freitas, Marcus Vinícius Nora de Souza, Thatyana Rocha Alves Vasconcelos, Núbia Boechat, Antoniana Ursine Krettli
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  ABSTRACT: The antimalarial activity of combinations of mefloquine or artesunic acid with ciprofloxacin and other synthetic fluoroquinolone was tested in vitro against Plasmodium falciparum using a strain (BHz26/86) partially resistant to chloroquine and a resistant clone (W2); both are sensitive to mefloquine. Inhibition of parasite growth was measured in relation to controls without drugs, either by counting parasitemia in Giemsa-stained blood smears or by measuring the reduction in [(3)H]-hypoxanthine uptake. Combinations containing artesunic acid or mefloquine with ciprofloxacin had significant in vitro activity, inhibiting by more than 90% of the growth of both strains of P. falciparum at doses significantly lower than those of the antimalarials alone. When tested in mice inoculated with P. berghei chloroquine-sensitive parasites (NK65 strain), ciprofloxacin was inactive, whereas mefloquine and artesunic acid were active (IC(50)=2.5 and 4.2 mg/kg, respectively); combinations containing mefloquine at an equivalent dose of 0.5 mg/kg reduced parasitemia by 59% and artesunic acid activity was also improved by ciprofloxacin. Our data support the idea that ciprofloxacin in combination with antimalarials may be useful in the treatment of chloroquine-resistant human malaria, allowing the use of lower doses of these drugs.
  European Journal of Pharmacology 04/2007; 558(1-3):194-8. · 2.52 Impact Factor