RESUMEN
A total of 39 endophytic fungi have been isolated from Viguiera arenaria and Tithonia diversifolia, both collected in São Paulo State, Brazil. The isolates were identified based on their ribosomal DNA sequences. The ethyl acetate (EtOAc) extracts of all endophytic fungi were evaluated for their antimicrobial, antiparasitic and antitumoral activity. Antimicrobial screening was conducted using an agar diffusion assay against three pathogenic microorganisms: Staphylococcus aureus, Escherichia coli and Candida albicans. Antiparasitic activity was determined by enzymatic inhibition of gGAPDH of Trypanosoma cruzi and adenine phosphorybosiltransferase (APRT) of Leishmania tarentolae. Antitumoral activity was tested against human T leukemia cells by the Mosmann colorimetric method. All extracts showed activity in at least one assay: 79.5% of the extracts were cytotoxic against leukemia cells, 5.1% of the extracts were active against S. aureus, 25.6% against E. coli and 64.1% against Candida albicans. Only one extract showed promising results in the inhibition of parasitic enzymes gGAPDH (95.0%) and three were found to inhibit APRT activity. The cytotoxic extract produced by the strain VA1 (Glomerella cingulata) was fractionated and yielded nectriapyrone and tyrosol. Nectriapyrone showed relevant cytotoxic activity against both human T leukemia and melanoma tumor cell lines.
Asunto(s)
Antibacterianos/farmacología , Antineoplásicos/farmacología , Antiparasitarios/farmacología , Asteraceae/microbiología , Hongos/química , Hongos/aislamiento & purificación , Adenina Fosforribosiltransferasa/antagonistas & inhibidores , Animales , Antibacterianos/aislamiento & purificación , Antineoplásicos/aislamiento & purificación , Antiparasitarios/aislamiento & purificación , Brasil , Candida albicans/efectos de los fármacos , ADN Espaciador Ribosómico/química , ADN Espaciador Ribosómico/genética , Escherichia coli/efectos de los fármacos , Hongos/clasificación , Hongos/genética , Gliceraldehído-3-Fosfato Deshidrogenasa (Fosforilante)/antagonistas & inhibidores , Humanos , Células Jurkat/efectos de los fármacos , Leishmania/enzimología , Melanoma , Pruebas de Sensibilidad Microbiana , Alcohol Feniletílico/análogos & derivados , Alcohol Feniletílico/aislamiento & purificación , Proteínas Protozoarias/antagonistas & inhibidores , Análisis de Secuencia de ADN , Staphylococcus aureus/efectos de los fármacos , Trypanosoma cruzi/enzimologíaRESUMEN
Three new disulfated meroterpenoids, ilhabelanol (1), ilhabrene (2), and isoakaterpin (3), have been isolated from extracts of the Brazilian marine sponge Callyspongia sp. Isoakaterpin (3) inhibits Leishmania spp. adenosine phosphoribosyl transferase with an IC50 of 1.05 microM. The structures of 1, 2, and 3 were elucidated by analysis of one- and two-dimensional NMR data. Ilhabelanol (1) and ilhabrene (2) both have unprecedented meroterpenoid carbon skeletons.
Asunto(s)
Adenina Fosforribosiltransferasa/antagonistas & inhibidores , Callyspongia/química , Inhibidores Enzimáticos/química , Terpenos/química , Animales , Inhibidores Enzimáticos/aislamiento & purificación , Inhibidores Enzimáticos/farmacología , Leishmania/enzimología , Conformación Molecular , Estereoisomerismo , Relación Estructura-Actividad , Terpenos/aislamiento & purificación , Terpenos/farmacologíaRESUMEN
Adenine phosphoribosyltransferase (APRT) enzyme from Leishmania tarentolae has been proposed as a target for the rational search of new leishmanicidal drugs. In this paper, we describe the evaluation of the inhibitory activity on L. tarentolae APRT enzyme of 46 crude extracts of Meliaceae and Rutaceae plants, besides three furoquinolone alkaloids. The results showed that 21 extracts were able to decrease the APRT enzymatic activity (IA% > or = 50). The methanolic extracts from roots and leaves of Cedrela fissilis and from fruits, branches and leaves of Cipadessa fruticosa have showed strong activities. Therefore, these species could be a promising source of lead compounds for the rational design of new leishmanicidal drugs. The phytochemical investigation of an active fraction from Almeidea rubra afforded the alkaloids isodutaduprine, isoskimmianine and isokokusagine, which showed low to moderate activity on APRT.