Antimicrobial Activity, in silico Molecular Docking, ADMET and DFT Analysis of Secondary Metabolites from Roots of Three Ethiopian Medicinal Plants.

BACKGROUND: Uvaria scheffleri (Annonaceae), Clematis burgensis (Ranunculaceae), and Euphorbia schimperiana (Euphorbiaceae) are medicinal plants traditionally used to treat cough, tuberculosis, asthma, sore throat and skin infections. METHODS: Silica gel column chromatographic separation was used to isolate compounds. Crude extract and isolated compounds were evaluated for antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Candida albicans via the broth dilution method. Docking studies were performed with E. coli DNA-Gyrase B and human DNA topoisomerase IIα by using AutoDock Vina. ADMET were predicted by SwissADME, PreADMET, and OSIRIS Property predictions. The optimized structures and molecular electrostatic potential surface of the isolated compounds were predicted by DFT analysis using B3LYP/6-31G basis levels. RESULTS: Silica gel column chromatographic separation afforded five compounds 1-5 of which N-methyl-2,3-bis(2-hydroxybenzyl)-1Н-indol (1) is reported herein for the first time, along with known C-benzylated dihydrochalcone uvaretin (2), bis(2-ethylheptyl) phthalate (3), lupeol (4) and suberosin derivative (5). Dichloromethane roots extract of U. scheffleri showed potent antibacterial activity against S. aureus (MIC = 6.25 µg/mL) compared to gentamicin (MIC=5 µg/mL). In silico, molecular docking analysis of compounds (1and 3-5) showed strong interaction with E. coli DNA gyrase B with a binding energy value ranging from -6.9 to -6.0 kcal/mol compared to ciprofloxacin -7.2 kcal/mol, whereas analysis against human topoisomerase IIα showed binding energy value ranging from -5.9 to -5.3 kcal/mol compared to vosaroxin (-6.2 kcal/mol). CONCLUSION: The results obtained suggest that N-methyl-2,3-bis(2-hydroxybenzyl)-1Н-indol (1) and coumarin (5) are potential topoisomerase II α inhibitors and might be used as anticancer agents. The ADMET studies showed the highest drug-likeness properties for studied compounds other than bis(2-ethylheptyl) phthalate (3). DFT calculations suggested that studied compounds showed the lowest gap energy and were chemically reactive, and isolated compounds may serve as potential drug candidates that corroborate with the traditional uses of studied plants.

Combination of an AccQ•Tag-Ultra-Performance Liquid Chromatographic Method with Tandem Mass Spectrometry for the Analysis of Amino Acids.

Amino acid analysis is a powerful tool in life sciences. Current analytical methods used for the detection and quantitation of low abundance amino acids in complex samples face intrinsic challenges such as insufficient sensitivity, selectivity, and throughput. This chapter describes a protocol that makes use of AccQ•Tag chemical derivatization combined with the exceptional chromatographic resolution of ultra-performance liquid chromatography (UPLC) and the sensitivity and selectivity of tandem mass spectrometry (MS/MS). The method has been fully implemented and validated using different tandem quadrupole detectors and thoroughly tested for a variety of samples such as P. falciparum, human red blood cells, and Arabidopsis thaliana extracts. Compared to currently available methods for amino acid analysis, the AccQ•Tag UPLC-MS/MS method presented here provides enhanced sensitivity and reproducibility and offers excellent performance within a short analysis time and a broad dynamic range of analyte concentration. The focus of this chapter is the application of this improved protocol for the compositional amino acid analysis in Arabidopsis thaliana leaf extracts using the Xevo TQ for mass spectrometric detection.

Pseudoxandra sclerocarpa maas, colombian medicinal plant: a review / Pseudoxandra sclerocarpa maas, planta medicinal colombiana: una revisión

The Annonaceae family is one of the largest, with 130 genre and 2500 species, consisting of trees, shrubs and a few vines. Within this family, the Pseudoxandra genus of neotropical distribution is found. In Colombia, there are endemic and native species, distributed in the Amazon region and along the valley of the Magdalena River in the Chocó. Of the total of 22 species that form the genus in Colombia, Pseudoxandra sclerocarpa Maas is exclusive of the Antioquia region, receiving the common name of garrapato or frisolo. From this tree, bisbenzylisoquinolinic alkaloids like antioquine, medellline, obaberine, among others, has been isolated. Also neolignans: dieugenol and dehydro-1-O-methydehydrodieugenol. It is used in traditional medicine as an antiparasitic. From the pharmacological point of view, the alkaloids have shown activity against leishmaniasis and also have spasmolytic activity. Within the bisbenzylisoquinolinic alkaloids, antioquine has properties of being calcium antagonist.

La familia Annonaceae es uno de los más grandes, con 130 géneros y 2.500 especies, que consiste en árboles, arbustos y algunos bejucos. Dentro de esta familia, el género Pseudoxandra es de distribución neotropical. En Colombia existen especies endémicas y nativas, distribuidas en la región del Amazonas ya lo largo del valle del río Magdalena en el Chocó. Del total de 22 especies que forman el género en Colombia, Pseudoxandra sclerocarpa es exclusiva de la región de Antioquia, recibiendo el nombre común de garrapato o frisolo. De este árbol se ha aislado alcaloides bisbencilisoquinolínicos como antioquina, medelllina, obaberina, entre otros. También neolignanos: dieugenol y dehidro-1-O-metil-dehidrodieugenol. Se utiliza en la medicina tradicional como un antiparasitario. Desde el punto de vista farmacológico, los alcaloides han mostrado actividad contra la leishmaniasis y también tienen actividad espasmolítica. Dentro de los alcaloides bisbencilisoquinolínicos, antioquina tiene propiedades de ser antagonista del calcio.

Annomontine, an alkaloid isolated from Annona purpurea, has anxiolytic-like effects in the elevated plus-maze.

The effects of annomontine, a pyrimidine- ß-carboline alkaloid isolated from the root of ANNONA PURPUREA, on anxiety was studied in mice using the elevated plus-maze. The behavioral effects of this alkaloid on the pentobarbital-induced hypnosis, the locomotor activity in an open field, and the motor coordination in the rotarod test were also evaluated. The intraperitoneal injection of annomontine (1-30 mg/kg) increased in a dose-dependent way the number of visits to and the time spent in the open arms of the elevated plus-maze in comparison to the control animals. Such effects were blocked by the prior application of flumazenil (3 mg/kg; i. p.), a specific antagonist for the binding of benzodiazepines on the GABA (A) receptor. Under the same experimental conditions annomontine failed to affect the behavior of the animals in the pentobarbital-induced hypnosis test and had no effects on locomotion and motor coordination. These results suggest that annomontine possesses anxiolytic-like effects which may be mediated at the level of the benzodiazepine binding site on the GABA (A) receptor.

Metabolomics for plant stress response.

Stress in plants could be defined as any change in growth condition(s) that disrupts metabolic homeostasis and requires an adjustment of metabolic pathways in a process that is usually referred to as acclimation. Metabolomics could contribute significantly to the study of stress biology in plants and other organisms by identifying different compounds, such as by-products of stress metabolism, stress signal transduction molecules or molecules that are part of the acclimation response of plants. These could be further tested by direct measurements, correlated with changes in transcriptome and proteome expression and confirmed by mutant analysis. In this review, we will discuss recent application of metabolomics and system biology to the area of plant stress response. We will describe approaches such as metabolic profiling and metabolic fingerprinting as well as combination of different 'omics' platforms to achieve a holistic view of the plant response stress and conduct detailed pathway analysis.

Bisbenzyltetrahydroisoquinolines, a new class of inhibitors of the mitochondrial respiratory chain complex I.

Four bisbenzyltetrahydroisoquinoline alkaloids (-)-medelline, (+)-antioquine, (+)-aromoline, and (+)-obamegine were isolated from the fruits of Xylopia columbiana. These compounds, the previously isolated alkaloids (+)-thaligrisine and (+)-isotetrandrine, as well as their O-acetylated derivatives were assayed on submitochondrial particles from beef heart as inhibitors of the mammalian respiratory chain. The results revealed that these alkaloids act as selective inhibitors of mitochondrial complex I in a 0.15 - 4.71 microM range. O-Acetylation, which increases their lipophilicity, considerably increased the inhibitory potency.

Selective action of acetogenin mitochondrial complex I inhibitors.

Five annonaceous acetogenins, rolliniastatin-1 [structure: see text], rolliniastatin-2 [structure: see text], laherradurin [structure: see text], squamocin [structure: see text], annonacin [structure: see text], and rotenone as a reference, differing in their NADH oxidase inhibition activity, have been evaluated for antifeedant, insecticidal, trypanocidal and cytotoxic effects on insect, mammalian and tumor cells. All the test compounds were toxic to Leptinotarsa decemlineata, demonstrated selective cytotoxicity to insect Sf9 cells and a panel of tumor cell lines with the multidrug-resistant SW480 (P-glycoprotein+, Pgp+) being the most sensitive one. Compounds [structure: see text] and rotenone had post-ingestive effects against Spodoptera littoralis larvae while [structure: see text] and rotenone were active against Trypanosoma cruzi. Based on their biochemical properties (inhibition of the mitochondrial NADH oxidase activity), the in vivo effects of these compounds on S. littoralis and their cytotoxic effects on Sf9 and tumor cells were more predictable than their effect on T. cruzi and mammalian cells.