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1.
Mem Inst Oswaldo Cruz ; 107(7): 859-66, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23147140

ABSTRACT

Artemisinin is the active antimalarial compound obtained from the leaves of Artemisia annua L. Artemisinin, and its semi-synthetic derivatives, are the main drugs used to treat multi-drug-resistant Plasmodium falciparum (one of the human malaria parasite species). The in vitro susceptibility of P. falciparum K1 and 3d7 strains and field isolates from the state of Amazonas, Brazil, to A. annua infusions (5 g dry leaves in 1 L of boiling water) and the drug standards chloroquine, quinine and artemisinin were evaluated. The A. annua used was cultivated in three Amazon ecosystems (várzea, terra preta de índio and terra firme) and in the city of Paulínia, state of São Paulo, Brazil. Artemisinin levels in the A. annua leaves used were 0.90-1.13% (m/m). The concentration of artemisinin in the infusions was 40-46 mg/L. Field P. falciparum isolates were resistant to chloroquine and sensitive to quinine and artemisinin. The average 50% inhibition concentration values for A. annua infusions against field isolates were 0.11-0.14 µL/mL (these infusions exhibited artemisinin concentrations of 4.7-5.6 ng/mL) and were active in vitro against P. falciparum due to their artemisinin concentration. No synergistic effect was observed for artemisinin in the infusions.


Subject(s)
Antimalarials/pharmacology , Artemisia annua/chemistry , Plant Extracts/pharmacology , Plasmodium falciparum/drug effects , Artemisinins/pharmacology , Brazil , Chloroquine/pharmacology , Drug Synergism , Inhibitory Concentration 50 , Parasitic Sensitivity Tests/methods , Quinine/pharmacology
2.
Mem. Inst. Oswaldo Cruz ; 107(7): 859-866, Nov. 2012. ilus, graf, tab
Article in English | LILACS | ID: lil-656040

ABSTRACT

Artemisinin is the active antimalarial compound obtained from the leaves of Artemisia annua L. Artemisinin, and its semi-synthetic derivatives, are the main drugs used to treat multi-drug-resistant Plasmodium falciparum (one of the human malaria parasite species). The in vitro susceptibility of P. falciparum K1 and 3d7 strains and field isolates from the state of Amazonas, Brazil, to A. annua infusions (5 g dry leaves in 1 L of boiling water) and the drug standards chloroquine, quinine and artemisinin were evaluated. The A. annua used was cultivated in three Amazon ecosystems (várzea, terra preta de índio and terra firme) and in the city of Paulínia, state of São Paulo, Brazil. Artemisinin levels in the A. annua leaves used were 0.90-1.13% (m/m). The concentration of artemisinin in the infusions was 40-46 mg/L. Field P. falciparum isolates were resistant to chloroquine and sensitive to quinine and artemisinin. The average 50% inhibition concentration values for A. annua infusions against field isolates were 0.11-0.14 μL/mL (these infusions exhibited artemisinin concentrations of 4.7-5.6 ng/mL) and were active in vitro against P. falciparum due to their artemisinin concentration. No synergistic effect was observed for artemisinin in the infusions.


Subject(s)
Antimalarials/pharmacology , Artemisia annua/chemistry , Plant Extracts/pharmacology , Plasmodium falciparum/drug effects , Artemisinins/pharmacology , Brazil , Chloroquine/pharmacology , Drug Synergism , Parasitic Sensitivity Tests/methods , Quinine/pharmacology
3.
Chem Biol Drug Des ; 79(5): 790-7, 2012 May.
Article in English | MEDLINE | ID: mdl-22284812

ABSTRACT

Dihydroperoxides and tetraoxanes derived from symmetrically substituted bis(arylmethyl)acetones were synthesized in modest to good yields using several methods. Three of these compounds exhibit an important in vitro antimalarial activity (1.0 µm ≤ IC(50) ≤ 5.0 µm) against blood forms of the human malaria parasite Plasmodium falciparum.


Subject(s)
Antimalarials/chemistry , Antimalarials/pharmacology , Peroxides/chemistry , Peroxides/pharmacology , Plasmodium falciparum/drug effects , Tetraoxanes/chemistry , Tetraoxanes/pharmacology , Acetone/chemical synthesis , Acetone/chemistry , Acetone/pharmacology , Antimalarials/chemical synthesis , Humans , Inhibitory Concentration 50 , Malaria, Falciparum/drug therapy , Peroxides/chemical synthesis , Structure-Activity Relationship , Tetraoxanes/chemical synthesis
4.
Phytother Res ; 25(8): 1181-8, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21302338

ABSTRACT

4-Nerolidylcatechol (4-NC) isolated from Piper peltatum L. (Piperaceae) was evaluated for in vitro antiplasmodial activity against Plasmodium falciparum (cultures of both standard CQR (K1) and CQS (3D7) strains and two Amazonian field isolates) and for in vivo antimalarial activity using the Plasmodium berghei-murine model. 4-NC exhibits significant in vitro and moderate in vivo antiplasmodial activity. 4-NC administered orally and subcutaneously at doses of 200, 400 and 600 mg/kg/day suppressed the growth of P. berghei by up to 63% after four daily treatments (days 1-4). Also, 4-NC exhibited important in vitro antiplasmodial activity against both standard and field P. falciparum strains in which 50% inhibition of parasite growth (IC(50) ) was produced at concentrations of 0.05-2.11 µg/mL and depended upon the parasite strain. Interestingly, healthy (non-infected) mice that received 4-NC orally presented (denatured) blood plasma which exhibited significant in vitro activity against P. falciparum. This is evidence that mouse metabolism allows 4-NC or active metabolites to enter the blood. Further chemical and pharmacological studies are necessary to confirm the potential of 4-NC as a new antimalarial prototype.


Subject(s)
Antimalarials/pharmacology , Catechols/pharmacology , Malaria/drug therapy , Piper/chemistry , Plasmodium berghei/drug effects , Plasmodium falciparum/drug effects , Animals , Brazil , Disease Models, Animal , Female , Malaria/blood , Malaria/parasitology , Malaria, Falciparum/blood , Malaria, Falciparum/drug therapy , Malaria, Falciparum/parasitology , Mice
5.
Eur J Med Chem ; 44(6): 2731-5, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19084293

ABSTRACT

4-Nerolidylcatechol (1) was isolated from cultivated Pothomorphe peltata root on a multigram scale using straight-forward solvent extraction-column chromatography. New semi-synthetic derivatives of 1 were prepared and tested in vitro against multidrug-resistant Plasmodium falciparum K1 strain. Mono-O-methyl, mono-O-benzyl, O,O-dibenzyl and O,O-dibenzoyl derivatives 2-8 exhibited IC(50) in the 0.67-22.52 microM range. Mono-O-methyl ethers 6 and 7 inhibited the in vitro growth of human tumor cell lines HCT-8 (colon carcinoma), SF-295 (central nervous system), LH-60 (human myeloblastic leukemia) and MDA/MB-435 (melanoma). In general, derivatives 2-8 are more stable to light, air and pH at ambient temperatures than their labile, natural precursor 1. These derivatives provide leads for the development of a novel class of antimalarial drugs with enhanced chemical and pharmacological properties.


Subject(s)
Antimalarials/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Catechols/pharmacology , Plant Extracts/pharmacology , Plasmodium falciparum/drug effects , Animals , Antimalarials/chemical synthesis , Antimalarials/chemistry , Antimalarials/toxicity , Antineoplastic Agents, Phytogenic/chemical synthesis , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/toxicity , Catechols/chemical synthesis , Catechols/chemistry , Catechols/toxicity , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Resistance , Drug Screening Assays, Antitumor , HL-60 Cells , Humans , Molecular Structure , Parasitic Sensitivity Tests , Piperaceae/chemistry , Plant Extracts/chemical synthesis , Plant Extracts/chemistry , Plant Extracts/toxicity , Plant Roots/chemistry , Stereoisomerism
6.
Rev Soc Bras Med Trop ; 41(4): 381-5, 2008.
Article in Portuguese | MEDLINE | ID: mdl-18853011

ABSTRACT

The routine test for diagnosing malaria is still the thick blood smear, despite its known decreased sensitivity and specificity in situations of low parasite density and mixed infections. The polymerase chain reaction is increasingly being used for molecular detection and identification of Plasmodium species, due to its higher sensitivity and specificity. Nested PCR was performed on whole-blood samples from 344 patients with acute febrile syndrome who came to a tertiary healthcare center in Manaus (State of Amazonas) for diagnostic confirmation of malaria. No malaria cases caused by Plasmodium malariae were detected through the blood smear or PCR. Co-positivity of 96.7%, co-negativity of 62.2% and kappa coefficient of 0.44 were observed between PCR and thick blood smear for Plasmodium falciparum. For Plasmodium vivax, co-positivity of 100%, co-negativity of 78.1% and kappa coefficient of 0.56 were observed. For mixed infection, co-positivity of 100%, co-negativity of 84.9% and kappa coefficient of 0.26 were observed. Polymerase chain reaction detected a high number of mixed infections in the samples analyzed, but its routine use for diagnosing malaria still deserves further discussion.


Subject(s)
DNA, Protozoan/genetics , Endemic Diseases , Malaria/diagnosis , Plasmodium falciparum/genetics , Plasmodium malariae/genetics , Plasmodium vivax/genetics , Polymerase Chain Reaction/methods , Animals , Brazil/epidemiology , Humans , Malaria/epidemiology , Malaria/parasitology , Plasmodium falciparum/isolation & purification , Plasmodium malariae/isolation & purification , Plasmodium vivax/isolation & purification , Sensitivity and Specificity
7.
Rev. Soc. Bras. Med. Trop ; 41(4): 381-385, jul.-ago. 2008. ilus, tab
Article in Portuguese | LILACS | ID: lil-494493

ABSTRACT

O exame de rotina para o diagnóstico da malária continua sendo a gota espessa, apesar da comprovada diminuição da sensibilidade e especificidade em situações de densidade parasitária baixa e infecções mistas. A reação em cadeia da polimerase vem sendo cada vez mais utilizada para a detecção molecular e identificação das espécies de plasmódio, por apresentar maior sensibilidade e especificidade. Foi realizada a nested-PCR em amostras de sangue total de 344 pacientes com síndrome febril aguda que se apresentaram para o diagnóstico de malária, em uma unidade terciária de saúde, em Manaus (Amazonas). Nenhum caso de malária por Plasmodium malariae foi diagnosticado à gota espessa ou PCR. Observou-se co-positividade de 96,7 por cento, co-negatividade de 62,2 por cento e coeficiente kappa de 0,44 entre PCR e gota espessa para Plasmodium falciparum. Para Plasmodium vivax, co-positividade de 100 por cento, co-negatividade de 78,1 por cento e coeficiente kappa de 0,56. Na detecção da malária mista, co-positividade de 100 por cento, co-negatividade de 84,9 por cento e coeficiente kappa de 0,26. A reação em cadeia da polimerase detectou alto número de infecções mistas nas amostras analisadas, mas seu uso rotineiro no diagnóstico da malária merece ainda ampla discussão.


The routine test for diagnosing malaria is still the thick blood smear, despite its known decreased sensitivity and specificity in situations of low parasite density and mixed infections. The polymerase chain reaction is increasingly being used for molecular detection and identification of Plasmodium species, due to its higher sensitivity and specificity. Nested PCR was performed on whole-blood samples from 344 patients with acute febrile syndrome who came to a tertiary healthcare center in Manaus (State of Amazonas) for diagnostic confirmation of malaria. No malaria cases caused by Plasmodium malariae were detected through the blood smear or PCR. Co-positivity of 96.7 percent, co-negativity of 62.2 percent and kappa coefficient of 0.44 were observed between PCR and thick blood smear for Plasmodium falciparum. For Plasmodium vivax, co-positivity of 100 percent, co-negativity of 78.1 percent and kappa coefficient of 0.56 were observed. For mixed infection, co-positivity of 100 percent, co-negativity of 84.9 percent and kappa coefficient of 0.26 were observed. Polymerase chain reaction detected a high number of mixed infections in the samples analyzed, but its routine use for diagnosing malaria still deserves further discussion.


Subject(s)
Animals , Humans , DNA, Protozoan/genetics , Endemic Diseases , Malaria/diagnosis , Plasmodium falciparum/genetics , Plasmodium malariae/genetics , Plasmodium vivax/genetics , Polymerase Chain Reaction/methods , Brazil/epidemiology , Malaria/epidemiology , Malaria/parasitology , Plasmodium falciparum/isolation & purification , Plasmodium malariae/isolation & purification , Plasmodium vivax/isolation & purification , Sensitivity and Specificity
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