Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Ano de publicação
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
Exp Parasitol ; 194: 67-78, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30268422

RESUMO

Treatment of drug resistant protozoa, bacteria, and viruses requires new drugs with alternative chemotypes. Such compounds could be found from Southeast Asian medicinal plants. The present study examines the cytotoxic, antileishmanial, and antiplasmodial effects of 11 ethnopharmacologically important plant species in Malaysia. Chloroform extracts were tested for their toxicity against MRC-5 cells and Leishmania donovani by MTT, and chloroquine-resistant Plasmodium falciparum K1 strain by Histidine-Rich Protein II ELISA assays. None of the extract tested was cytotoxic to MRC-5 cells. Extracts of Uvaria grandiflora, Chilocarpus costatus, Tabernaemontana peduncularis, and Leuconotis eugenifolius had good activities against L. donovani with IC50 < 50 µg/mL. Extracts of U. grandiflora, C. costatus, T. peduncularis, L. eugenifolius, A. subulatum, and C. aeruginosa had good activities against P. falciparum K1 with IC50 < 10 µg/mL. Pinoresinol isolated from C. costatus was inactive against L. donovani and P. falciparum. C. costatus extract and pinoresinol increased the sensitivity of Staphylococcus epidermidis to cefotaxime. Pinoresinol demonstrated moderate activity against influenza virus (IC50 = 30.4 ±â€¯11 µg/mL) and was active against Coxsackie virus B3 (IC50 = 7.1 ±â€¯3.0 µg/mL). ß-Amyrin from L. eugenifolius inhibited L. donovani with IC50 value of 15.4 ±â€¯0.01 µM. Furanodienone from C. aeruginosa inhibited L. donovani and P. falciparum K1 with IC50 value of 39.5 ±â€¯0.2 and 17.0 ±â€¯0.05 µM, respectively. Furanodienone also inhibited the replication of influenza and Coxsackie virus B3 with IC50 value of 4.0 ±â€¯0.5 and 7.2 ±â€¯1.4 µg/mL (Ribavirin: IC50: 15.6 ±â€¯2.0 µg/mL), respectively. Our study provides evidence that medicinal plants in Malaysia have potentials as a source of chemotypes for the development of anti-infective leads.


Assuntos
Anti-Infecciosos/farmacologia , Leishmania donovani/efeitos dos fármacos , Medicina Tradicional do Leste Asiático/métodos , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Plasmodium falciparum/efeitos dos fármacos , Anti-Infecciosos/toxicidade , Apocynaceae/química , Linhagem Celular , Sinergismo Farmacológico , Enterovirus Humano B/efeitos dos fármacos , Etnofarmacologia/métodos , Furanos/química , Furanos/isolamento & purificação , Furanos/farmacologia , Furanos/toxicidade , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Concentração Inibidora 50 , Lignanas/química , Lignanas/isolamento & purificação , Lignanas/farmacologia , Lignanas/toxicidade , Malásia , Extratos Vegetais/química , Extratos Vegetais/toxicidade , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Sesquiterpenos/toxicidade , Tabernaemontana/química , Uvaria/química
2.
Malar J ; 10: 291, 2011 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-21981896

RESUMO

BACKGROUND: Plasmodium vivax is the most prevalent cause of human malaria in tropical regions outside the African continent. The lack of a routine continuous in vitro culture of this parasite makes it difficult to develop specific drugs for this disease. To facilitate the development of anti-P. vivax drugs, bacterial and yeast surrogate models expressing the validated P. vivax target dihydrofolate reductase-thymidylate synthase (DHFR-TS) have been generated; however, they can only be used as primary screening models because of significant differences in enzyme expression level and in vivo drug metabolism between the surrogate models and P. vivax parasites. METHODS: Plasmodium falciparum and Plasmodium berghei parasites were transfected with DNA constructs bearing P. vivax dhfr-ts pyrimethamine sensitive (wild-type) and pyrimethamine resistant (mutant) alleles. Double crossover homologous recombination was used to replace the endogenous dhfr-ts of P. falciparum and P. berghei parasites with P. vivax homologous genes. The integration of Pvdhfr-ts genes via allelic replacement was verified by Southern analysis and the transgenic parasites lines validated as models by standard drug screening assays. RESULTS: Transgenic P. falciparum and P. berghei lines stably expressing PvDHFR-TS replacing the endogenous parasite DHFR-TS were obtained. Anti-malarial drug screening assays showed that transgenic parasites expressing wild-type PvDHFR-TS were pyrimethamine-sensitive, whereas transgenic parasites expressing mutant PvDHFR-TS were pyrimethamine-resistant. The growth and sensitivity to other types of anti-malarial drugs in the transgenic parasites were otherwise indistinguishable from the parental parasites. CONCLUSION: With the permanent integration of Pvdhfr-ts gene in the genome, the transgenic Plasmodium lines expressing PvDHFR-TS are genetically stable and will be useful for screening anti-P. vivax compounds targeting PvDHFR-TS. A similar approach could be used to generate transgenic models specific for other targets of interest, thus facilitating the development of anti-P. vivax drugs in general.


Assuntos
Antimaláricos/isolamento & purificação , Antagonistas do Ácido Fólico/isolamento & purificação , Plasmodium berghei/enzimologia , Plasmodium falciparum/efeitos dos fármacos , Plasmodium vivax/efeitos dos fármacos , Tetra-Hidrofolato Desidrogenase/biossíntese , Timidilato Sintase/biossíntese , Antimaláricos/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos , Antagonistas do Ácido Fólico/farmacologia , Instabilidade Genômica , Humanos , Organismos Geneticamente Modificados , Plasmodium berghei/genética , Plasmodium falciparum/enzimologia , Plasmodium falciparum/genética , Plasmodium vivax/enzimologia , Plasmodium vivax/genética , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Recombinação Genética , Tetra-Hidrofolato Desidrogenase/genética , Timidilato Sintase/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA