RESUMEN
Streptomyces hygroscopicus UFPEDA 3370 was fermented in submerged cultivation and the biomass extract was partitioned, obtaining a fraction purified named EB1. After purification of EB1 fraction, nigericin free acid was obtained and identified. Nigericin presented cytotoxic activity against several cancer cell lines, being most active against HL-60 (human leukemia) and HCT-116 (human colon carcinoma) cell lines, presenting IC50 and (IS) values: 0.0014 µM, (30.0) and 0.0138 µM (3.0), respectively. On HCT-116, nigericin caused apoptosis and autophagy. In this study, nigericin was also screened both in vitro and in silico against a panel of cancer-related kinases. Nigericin was able to inhibit both JAK3 and GSK-3ß kinases in vitro and its binding affinities were mapped through the intermolecular interactions with each target in silico.
Asunto(s)
Antineoplásicos/farmacología , Neoplasias Colorrectales/patología , Nigericina/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Streptomyces/química , Antineoplásicos/química , Antineoplásicos/metabolismo , Apoptosis/efectos de los fármacos , Dominio Catalítico , Línea Celular Tumoral , Humanos , Janus Quinasa 3/antagonistas & inhibidores , Janus Quinasa 3/química , Janus Quinasa 3/metabolismo , Simulación del Acoplamiento Molecular , Nigericina/química , Nigericina/metabolismo , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/metabolismoRESUMEN
Chrysobalanus icaco L. is a native plant of Brazil used as a food source and traditionally for the treatment of various diseases. The aim of study was performed the phytochemical analysis by UPLC-DAD-ESI-QTOF-MS/MS, and evaluated acute and repeated dose oral toxicities of the C. icaco L. leaf aqueous extract (AECi). The acute toxicity study was performed using a dose of AECi 2000 mg/kg, while the repeated dose toxicity study, the AECi was administered daily at doses of 100, 200 and 400 mg/kg, for 28 days. Behavior and mortality of animals were observed during the test period and body weight, as well water and eating consumption. Hematological, biochemical parameters and histopathological examinations were carried out. Phytochemical analysis of the AECi revealed the presence of flavonoids and tannins. Oral single dose of 2000 mg/kg of AECi resulted in no mortalities or abnormal clinical signs. Studies of repeated dose toxicity promoted a reduction in the body weight of treated animals and an increase of hepatic enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in both, males and females. Histopathological analyzes showed alterations in the livers of animals treated with AECi. Thus, this study recommends the population take care when using this species, especially during prolonged periods.
