Search Results (3)

Targeting cancer stem cells (CSCs) in anticancer discovery is very difficult due to the resistance of CSCs to conventional drugs, their low proliferation rate, improved DNA damage repair, and the overexpression of anti-apoptotic proteins and multidrug resistance transporters. Different CSC targets, such as the ABC cassette, surface markers, signal cascade, and tumour microenvironment, are involved in the interruption of cell signaling pathways that are critical for the survival and functioning of the CSC population. The study aims to identify potential drug-like phytotoxic alkaloids with anticancer activity from the toxic plants-phytotoxins (TPPTs) database. A total of 1586 phytotoxins were filtered to obtain 653 alkaloids. Lipinski’s properties and the TPSA of alkaloids were predicted for drug likeness and toxicity based on various organ endpoints. Compounds that obeyed Lipinski’s rule of five, with moderate or no toxicity and an LD₅₀ of >2000 mg/kg, were selected. The 12 drug-like phytotoxic alkaloids obtained from the filtering were docked on an isomerase-perdeuterated E65Q-TIM protein (ID: 7AZA; resolution = 1.10 Å) cocrystallized with phosphoglycolohydroxamate. The best binding poses were ranked using their binding energies (E) and inhibition constants (Ki). An evaluation of the protein—ligand’s best conformational poses allowed us to identify three alkaloids (norcoclaurine, palustridiene, and apovincamine) with Ki 1.00 µM and E −9.00 kcal/mol. All the docked ligands could bind more efficiently to the isomerase-perdeuterated E65Q-TIM protein than the co-crystallized phosphoglycolohydroxamate. Significant protein—ligand binding interactions also occurred for (-)-eburnamonine (E = −8.03 kcal/mol; Ki = 1.30 µM) and retamine (E = −7.81 kcal/mol; Ki = 1.89 µM). The efficient inhibition of perdeuterated E65Q-TIM in CSCs using phytotoxic alkaloids provided more insights into understanding the mechanisms of the anticancer activity of phytotoxic alkaloids. Full article

The most prominent horsetail species, Equisetum arvense, has an array of different medicinal properties, thus the proper authentication and differentiation of the plant from the more toxic Equisetum palustre is important. This study sought to identify different samples of E. arvense and E. palustre using three analytical methods. The first method involved the use of HPTLC analysis, as proposed by the European Pharmacopoeia. The second, HPLC-ESI-MS/MS, is capable of both identification and quantification and was used to determine the Equisetum alkaloid content in each sample. A third method was DNA barcoding, which identifies the samples based on their genetic make-up. Both HPTLC and HPLC-ESI-MS/MS proved to be suitable methods of identification, with HPLC-ESI-MS/MS proving the more sophisticated method for the quantification of alkaloids in the Equisetum samples and for determining the adulteration of E. arvense. For DNA barcoding, optimal primer pairs were elucidated to allow for the combined use of the rbcL and ITS markers to accurately identify each species. As new DNA marker sequences were added to GenBank, the reference library has been enriched for future work with these horsetail species. Full article

Marsh horsetail (Equisetum palustre L.) is one of the most poisonous plants of wet grasslands in the northern hemisphere, which poses a major health threat to livestock. Available data on the levels of its main alkaloids are currently contradictory due to the inadequate analytical methods and the wide variation in toxicity levels reported. Here, we tested the hypothesis that the ontogenetic stage of plant development may explain a significant part of the variations in the main Equisetum-type alkaloids. Two populations of marsh horsetail were sampled over two growing seasons. The plant material was classified according to their developmental stages and subsequently the main alkaloids were determined by hydrophilic interaction liquid chromatography and high-performance liquid chromatography electrospray tandem mass spectrometry (HILIC HPLC-ESI-MS/MS) analysis. ANOVA revealed significant effects of the ontogenetic stage but not the site on the main Equisetum-type alkaloids (sum of palustrine and palustridiene) ranging from 213 to 994 mg/kg dry matter (DM). The highest alkaloid content was found in the stages of early development. Not the season itself, but the growth temperature co-influenced the alkaloid content. Our results help to resolve the seemingly contradictory information provided by previous studies on the toxicity of E. palustre and are of practical relevance for the prevention of contamination risks in wet grassland use. Full article