RESUMEN
Ilhéus virus (ILHV) is a neglected mosquito-borne flavivirus. ILHV infection may lead to Ilhéus fever, an emerging febrile disease like dengue fever with the potential to evolve into a severe neurological disease characterized by meningoencephalitis; no specific treatments are available for this disease. This study assessed the antiviral properties of caffeic acid, an abundant component of plant-based food products that is also compatible with the socioeconomic limitations associated with this neglected infectious disease. The in vitro activity of caffeic acid on ILHV replication was investigated in Vero and A549 cell lines using plaque assays, quantitative RT-PCR, and immunofluorescence assays. We observed that 500 µM caffeic acid was virucidal against ILHV. Molecular docking indicated that caffeic acid might interact with an allosteric binding site on the envelope protein.
Asunto(s)
Antivirales , Animales , Humanos , Simulación del Acoplamiento Molecular , Células A549 , Sitio Alostérico , Antivirales/farmacologíaRESUMEN
The alkaloid ricinine (3-cyano-4-methoxy-N-methyl-2-pyridone) is found in different parts of the Ricinus communis plant and is known to possess several bioactive properties, including strong antioxidant activity. In this study, a new microwave-assisted extraction (MAE) method was developed for the recovery of ricinine from R. communis leaves. The extraction variables studied were extraction temperature (between 125 °C and 175 °C), microwave power (between 500 W and 1000 W), extraction time (between 5 min and 15 min), extraction solvent (between 10% and 90% of EtOAc in MeOH), and solvent-to-sample ratio (between 25:1 mL and 50:1 mL of solvent per gram of the sample). On studying the effects of extraction variables, both solvent and liquid-to-solid ratio were found to exhibit the highest effects on ricinine recovery. A fast (15 min) microwave-assisted extraction method was developed (high temperatures can be applied because the stability of ricinine is proven in the literature), allowing for the recovery of ricinine from R. communis leaves. The study revealed that R. communis leaves had almost 1.5 mg g-1 (dried weight) of ricinine.
RESUMEN
Cysteine proteinases (cathepsins) from Leishmania spp. are promising molecular targets against leishmaniasis. Leishmania mexicana cathepsin L is essential in the parasite life cycle and a pivotal in virulence factor in mammals. Natural products that have been shown to display antileishmanial activity were screened as part of our ongoing efforts to design inhibitors against the L. mexicana cathepsin L-like rCPB2.8. Among them, agathisflavone (1), tetrahydrorobustaflavone (2), 3-oxo-urs-12-en-28-oic acid (3), and quercetin (4) showed significant inhibitory activity on rCPB2.8 with IC50 values ranging from 0.43 to 18.03 µM. The mechanisms of inhibition for compounds 1-3, which showed Ki values in the low micromolar range (Ki = 0.14-1.26 µM), were determined. The biflavone 1 and the triterpene 3 are partially noncompetitive inhibitors, whereas biflavanone 2 is an uncompetitive inhibitor. The mechanism of action established for these leishmanicidal natural products provides a new outlook in the search for drugs against Leishmania.
Asunto(s)
Productos Biológicos/farmacología , Catepsina L/antagonistas & inhibidores , Leishmania mexicana/enzimología , Biflavonoides/farmacología , Catepsina B/antagonistas & inhibidores , Catepsina B/genética , Catepsina L/genética , Humanos , Concentración 50 Inhibidora , Cinética , Leishmania mexicana/genética , Quercetina/farmacología , Proteínas Recombinantes/efectos de los fármacos , Proteínas Recombinantes/genéticaRESUMEN
Byrsonima coccolobifolia leaf and stem extracts were studied in the search for possible leishmanicidal compounds using arginase (ARG) from Leishmania amazonensis as a molecular target. Flavonoids 1b, 1e-1g, 2a, 2b, and 2d-2f showed significant inhibitory activity, with IC50 values ranging from 0.9 to 4.8 µM. The kinetics of the most active compounds were determined. Flavonoids 1e, 1f, 2a, 2b, and 2e were characterized as noncompetitive inhibitors of ARG with dissociation constants (Ki) ranging from 0.24 to 3.8 µM, demonstrating strong affinity. Structure-activity relationship studies revealed some similarities in the structural features of flavonoids related to ARG activity.