Cyclopeptide Alkaloids from Discaria chacaye (Rhamnaceae) as Result of Symbiosis with Frankia (Actinomycetales).

Cyclopeptide alkaloids with different biological activities are present in plants of the family Rhamnaceae. Plants of this family grow in a symbiotic relationship with aerobic Gram-positive actinomycetes belonging to the genus Frankia. This goal of this research was a study of the comparative profile of alkaloids present in Discaria chacaye and to establish a connection between the presence or absence of Frankia sp. and the alkaloids. In addition, insecticidal activities of the alkaloidal extract were examined. A total of 24 alkaloids were identified, of which 12 have a benzylisoquinoline skeleton, 9 were cyclopeptides, 2 isoquinolines, and 1 aporphine. The presence of cyclopeptide alkaloids is associated with Frankia nodules in the plant root. The alkaloid extracts showed insecticidal activity with mortality dose-dependence and LD50 values between 44 to 71 µg/mL.

Assessments of Ceanothanes Triterpenes as Cholinesterase Inhibitors: An Investigation of Potential Agents with Novel Inspiration for Drug Treatment of Neurodegenerative Diseases.

The purpose of this study was to determine the inhibitory capacity of ceanothanes triterpenes isolate from Chilean Rhamnaceae on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Seven ceanothanes triterpenes were isolated from aerial parts of plant material by classical phytochemical methods or prepared by the hemisynthetic method. Structures were determined by the spectroscopic method (1H-NMR and 13C NMR) and mass spectrometry (MS). AChE and BChE activity were determined by the Ellmann method for all compounds. All tested compounds exerted a greater affinity to AChE than to BChE, where compound 3 has an IC50 of 0.126 uM for AChE and of >500 uM to BChE. Kinetic studies indicated that its inhibition was competitive and reversible. According to the molecular coupling and displacement studies of the propidium iodide test, the inhibitory effect of compound 3 would be produced by interaction with the peripheral anionic site (PAS) of AChE. The compounds tested (1−7) showed an important inhibitory activity of AChE, binding to PAS. Therefore, inhibitors that bind to PAS would prevent the formation of the AChE-Aß complex, constituting a new alternative in the treatment of Alzheimer's disease (AD).

Dyhidro-ß-agarofurans natural and synthetic as acetylcholinesterase and COX inhibitors: interaction with the peripheral anionic site (AChE-PAS), and anti-inflammatory potentials.

In order to find molecules of natural origin with potential biological activities, we isolate and synthesise compounds with agarofuran skeletons (epoxyeudesmanes). From the seeds of Maytenus disticha and Maytenus magellanica we obtained six dihydro-ß-agarofurans, and by means of the Robinson annulation reaction we synthesised five compounds with the same skeleton. The structures were established on the basis of NMR, IR, and MS. The evaluated compounds showed inhibitory activity on the acetylcholinesterase enzyme and on the COX enzymes. Compound 4 emerged as the most potent in the acetylcholinesterase inhibition assay with IC50 17.0 ± 0.016 µM on acetylcholinesterase (AChE). The compounds evaluated were shown to be selective for AChE. The molecular docking, and the propidium displacement assay suggested that the compounds do not bind to the active site of the enzyme AChE, but rather bind to the peripheral anionic site (PAS) of the enzyme, on the other hand, the natural compound 8, showed the best inhibitory activity on the COX-2 enzyme with an IC50 value of 0.04 ± 0.007 µM. The pharmacokinetic profile calculated in silico using the SWISSADME platform shows that these molecules could be considered as potential drugs for the treatment of neurodegenerative diseases such as AD.

Assessment of Insecticidal Activity of Benzylisoquinoline Alkaloids from Chilean Rhamnaceae Plants against Fruit-Fly Drosophila melanogaster and the Lepidopteran Crop Pest Cydia pomonella.

The Chilean plants Discaria chacaye, Talguenea quinquenervia (Rhamnaceae), Peumus boldus (Monimiaceae), and Cryptocarya alba (Lauraceae) were evaluated against Codling moth: Cydia pomonella L. (Lepidoptera: Tortricidae) and fruit fly Drosophila melanogaster (Diptera: Drosophilidae), which is one of the most widespread and destructive primary pests of Prunus (plums, cherries, peaches, nectarines, apricots, almonds), pear, walnuts, and chestnuts, among other. Four benzylisoquinoline alkaloids (coclaurine, laurolitsine, boldine, and pukateine) were isolated from the above mentioned plant species and evaluated regarding their insecticidal activity against the codling moth and fruit fly. The results showed that these alkaloids possess acute and chronic insecticidal effects. The most relevant effect was observed at 10 µg/mL against D. melanogaster and at 50 µg/mL against C. pomonella, being the alteration of the feeding, deformations, failure in the displacement of the larvae in the feeding medium of D. melanogaster, and mortality visible effects. In addition, the docking results show that these type of alkaloids present a good interaction with octopamine and ecdysone receptor showing a possible action mechanism.

Identification of structurally diverse alkaloids in Talguenea quinquinervia (gill. Et hook) by liquid chromatography/electrospray ionisation tandem mass spectroscopy and insecticidal activity.

INTRODUCTION: Talguenea quinquinervia has been used in folk medicine and to dye wool, and the main constituents are alkaloids and triterpenes. Identification of these type of compounds in this specie is a necessary step to understand the biological properties. OBJECTIVE: To evaluate the relationship between the chemical composition of root from T. quinquinervia and its insecticidal properties using liquid chromatography electrospray ionisation tandem mass spectrometry (LC-ESI-MS/MS). METHODS: Alkaloids were extracted using Soxhlet extraction with methanol. Total extract was partitioned at pH 2 and 12 to enrich alkaloid constituents and to remove interferences. The separation of alkaloids in the Talguenea extract was performed on a C18 column using gradient elution and their tandem mass spectra were obtained by quadrupole time-of-flight tandem mass spectrometry (QTOF-MS/MS) to perform accurate mass measurements of fragment ions for the alkaloid constituents. RESULTS: Several types of alkaloids were separated and identified by LC-ESI-MS/MS. The structural assignment of individual alkaloids was performed based on convergence of MS/MS spectral data, pH partitioning behaviour, LC retention behaviour, and accurate mass measurements. The pH partition of the extract provided structural information about unknown alkaloids extracted from T. quinquinervia. A total of 20 compounds were identified and tentatively characterised, and of these 15 alkaloids were reported for the first time in the investigated T. quinquinervia. CONCLUSION: The chemical profiling of alkaloids in T. quinquinervia with different origins was performed for the first time and provided diagnostic ions for diverse alkaloids in T. quinquinervia. Insecticidal activity observed can be explain by the presence of alkaloid and pentacyclic triterpenes on the fractions assayed.