Caerulines A and B, Flavonol Diacylglycosides from Persea caerulea.

Two undescribed 4'-O-methylkaempferol-[3″,4″-di-p-coumaroyl]-α-l-rhamnopyranosides, caerulines A and B (1-2), along with three known 4'-O-methylkaempferol diacylrhamnosides isomers (3-5) were isolated from an ethanol extract of the leaves of Persea caerulea, a native plant growing on the Colombian Caribbean coast. The chemical structures of 1 and 2 were elucidated by spectroscopic methods. The effect of compounds 1-5 against four pathogenic microorganisms [i.e., methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter baumannii, Candida albicans, and Aspergillus fumigatus] was tested in vitro. The compounds exhibited no activity against these pathogens except MRSA (MIC 12-48 µg/mL). Caeruline B (2) was found to be the most active compound with a modest anti-MRSA activity (MIC = 12 µg/mL).

Chemical and Antifungal Variability of Several Accessions of Azadirachta indica A. Juss. from Six Locations Across the Colombian Caribbean Coast: Identification of Antifungal Azadirone Limonoids.

Plant materials (i.e., leaves, fruits, and seeds) from 40 trees of Azadirachta indica A. Juss. were collected from six different locations across the Colombian Caribbean coast. Eighty-four ethanolic extracts were prepared and the total limonoid contents (TLiC) and the antifungal activity against Fusarium oxysporum conidia were measured. Their chemical profiles were also recorded via liquid chromatography-electrospray ionization interface-mass spectrometry (LC-ESI-MS) analysis and the top-ranked features were then annotated after supervised multivariate statistics. Inter-location chemical variability within sample set was assessed by sparse partial least squares discriminant analysis (sPLS-DA) and the chemical profiles and biological activity datasets were integrated through single-Y orthogonal partial least squares (OPLS) to identify antifungal bioactives in test extracts. The TLiC and antifungal activity (IC50 values) of the A. indica-derived extracts were found to be ranging from 4.5 to 48.5 mg limonin equivalent per g dry extract and 0.08-44.8 µg/mL, respectively. The presence/abundance of particular limonoids between collected samples influenced the variability among locations. In addition, the integration of chemical and antifungal activity datasets showed five features as markers probably contributing to the bioactivity, annotated as compounds with an azadirone-like moiety. To validate the information provided by the single-Y OPLS model, a high performance liquid chromatography (HPLC)-based microfractionation was then carried out on an active extract. The combined plot of chromatographic profile and microfraction bioactivity also evidenced five signals possessing the highest antifungal activity. The most active limonoid was identified as nimonol 1. Hence, this untargeted metabolite profiling was considered as a convenient tool for identifying metabolites as inter-location markers as well as antifungals against Fusarium oxysporum.

Bio-Guided Fractionation of Ethanol Extract of Leaves of Esenbeckia alata Kunt (Rutaceae) Led to the Isolation of Two Cytotoxic Quinoline Alkaloids: Evidence of Selectivity Against Leukemia Cells.

Bio-guided fractionation performed on the leaves-derived ethanol extract of Esenbeckia alata (Rutaceae), a plant used in traditional medicine, led to the isolation of two alkaloids, kokusaginine 1 and flindersiamine 2, as main cytotoxic agents. Primary ethanolic extract and raw fractions exhibited cell inhibition against five cancer cell lines at different levels (25-97% inhibition at 50 µg/mL) as well as isolated alkaloids 1-2 (30-90% inhibition at 20 µM). Although alkaloid 2 generally was the most active compound, both alkaloids showed a selective effect on K562, a human chronic myelogenous leukemia cell line. The E1-like ubiquitin-activating enzymes (e.g., UBA5) have been recently described as important targets for future treatment of cancer progression, such as leukemia, among others. Therefore, as a rationale to the observed cytotoxic selectivity, an in-silico evaluation by molecular docking and molecular dynamics was also explored. Compounds 1-2 exhibited good performance on the interaction within the active site of UBA5.

Actividad acaricida de extractos de lauráceas sobre los ácaros intradomiciliarios Dermatophagoides farinae y Blomia tropicalis / Acaricide activity of Lauraceae extracts agaisnt domiciliary mites Dermatophagoides farinae and Blomia tropicalis

Introducción: especies de la familia Lauraceae son fuentes importantes de sustancias bioactivas, como las que actúan de insecticidas. En los estudios de bioprospección de lauraceas colombianas, a siete especies medicinales pertenecientes a esta familia se les evaluó su actividad acaricida frente a Dermatophagoides farinae y Blomia tropicalis, considerados como un problema en salud pública a nivel intradomiciliario. Objetivo: determinar la actividad acaricida de los extractos etanólicos de las especies de Lauraceae sobre los ácaros intradomiciliarios Dermatophagoides farinae y Blomia tropicalis, así como caracterizar los extractos obtenidos mediante ensayo fitoquímico preliminar. Métodos: la actividad acaricida in vitro de los extractos de las siete especies, colectadas en diferentes regiones de Colombia, se evaluó sobre individuos adultos a través de las pruebas de contacto directo y acción fumigante. Cada uno de los extractos se caracterizó químicamente mediante ensayos de coloración o precipitación. Resultados: en la prueba de contacto, el extracto de hojas de Persea caerulea eliminó al 100 % de Dermatophagoides farinae. En la prueba de acción fumigante, el extracto de hojas de Persea caerulea, eliminó 100 % de Dermatophagoides farinae y 83,4 % de Blomia tropicalis (después de 120 min de exposición; a 0,1 mg/mL). El ensayo fitoquímico preliminar permitió identificar la posible presencia de metabolitos acorde con la quimiotaxonomía de las Lauraceae. Conclusiones: los resultados permiten sugerir que especies de la familia Lauraceae serían catalogados como fuente potencial de biocontroladores contra los ácaros domiciliarios Dermatophagoides farinae y Blomia tropicalis.

Introduction: Lauraceae plants are considered as important sources of bioactive substances, as those acting as insecticides. As part of our program for bioprospecting studies on Colombian Lauraceae plants, seven medicinal species belonging to this family were studied for their acaricide activity against Dermatophagoides farinae and Blomia tropicalis, considered public health problems at domiciliary level. Objective: to evaluate acaricide activity of ethanol extracts from Lauraceae plants on domiciliary mites Dermatophagoides farinae and Blomia tropicalis as well as to characterize ethanol-soluble extracts by preliminary phytochemical assay. Methods: in vitro acaricide activity of extracts from seven plants belonging to the Lauraceae family, harvested in different regions of Colombia, was assessed on individual adults through direct contact test and fumigant action. Each plant extract was tested for chemical characterization by means of coloration and precipitation tests. Results: in direct contact bioassay, the leaf extract from Persea caerulea eliminated 100 % of Dermatophagoides farinae. In fumigant action bioassay, the leaf extract of Persea caerulea eliminated 100 % Dermatophagoides farinae and 83.37 % of Blomia tropicalis (after 120 minutes exposure at 0.1 mg/mL). The preliminary phytochemical testing identified the possible presence of metabolites according to the Lauraceae chemotaxonomy. Conclusions: obtained results indicated that Lauraceae plants could be catalogued as a source of potential biocontrol agents against specific domiciliary mites Dermatophagoides farinae and Blomia tropicalis.