It is estimated that Trichomonas vaginalis affects an astonishing 3.9% of the world’s population, and while many of those infected are asymptomatic, progression of the disease can lead to serious health problems. Currently, the nitroimidazoles constitute the only drug class approved to treat trichomoniasis in the United States, which makes the spread of drug resistance a realistic concern. We developed a new image-based, high-throughput, and high-content assay for testing natural products (purified compounds and extracts) for antitrichomonal activity. Applying this assay system to a library of fungal natural product extracts led to the identification of three general classes of natural product inhibitors that exhibited moderate to strong activities against T. vaginalis: anthraquinones, xanthone–anthraquinone heterodimers, and decalin-linked tetramic-acid-containing metabolites. The tetramate natural products emerged as the most promising candidate molecules with pyrrolocin A (51) exhibiting potent activity against the parasite (EC50 = 60 nM), yet this metabolite showed limited toxicity to mammalian cell lines (selectivity index values of 100 and 167 versus 3T3 fibroblast and Ect1 normal cervical cells, respectively). The imaging-based assay system is a powerful tool for the bioassay-guided purification of single-component antitrichomonal biomolecules from complex natural product mixtures.

Recently, wheat has attracted attention as a functional food, rather than a simple dietary energy source. Accordingly, whole-grain intake increases with an understanding of bioactive phytochemicals in bran. The development of colored wheat has drawn more attention to the value of bran owing to its nutritional quality, as well as the antioxidant properties of the colorant. The present 1H NMR-based chemometric study evaluated the compositional improvement of radiation-induced mutants in purple wheat by focusing on the predominant metabolites with high polarity. A total of 33 metabolites, including three choline derivatives, three sugar alcohols, four sugars, 13 amino acids, eight organic acids, and two nucleosides, were identified throughout the 1H NMR spectra, and quantification data were obtained for the identified metabolites via peak shape-based quantification. Principal component and hierarchical cluster analyses were conducted for performing multivariate analyses. The colored original wheat was found to exhibit improvements compared to yellow wheat in terms of the contents of primary metabolites, thus highlighting the importance of conducting investigations of polar metabolites. The chemometrics studies further revealed mutant lines with a compositional enhancement for metabolites, including lysine, proline, acetate, and glycerol.

The barks of Eucommia ulmoides (Eucommiae Cortex, Eucommiaceae) have been used as a traditional medicine in Korea, Japan, and China to treat hypertension, reinforce the muscles and bones, and recover the damaged liver and kidney functions. Among these traditional uses, to establish the recovery effects on the damaged organs on the basis of phytochemistry, the barks of E. ulmoides have been investigated to afford three known phenolic compounds, coniferaldehyde glucoside (1), bartsioside (2), and feretoside (3), which were found in the family Eucommiaceae for the first time. The compounds 1-3 were evaluated for their inducible activities on the heat shock factor 1 (HSF1), and heat shock proteins (HSPs) 27 and 70, along with four compounds, geniposide (4), geniposidic acid (5), pinoresinol diglucoside (6), and liriodendrin (7), which were previously reported from E. ulmoides. Compounds 1-7 increased expression of HSF1 by a factor of 1.214, 1.144, 1.153, 1.114, 1.159, 1.041, and 1.167 at 3 μM, respectively. Coniferaldehyde glucoside (1) showed the most effective increase of HSF1 and induced successive expressions of HSP27 and HSP70 in a dose-dependent manner without cellular cytotoxicity, suggesting a possible application as a HSP inducer to act as cytoprotective agent.

The structures of four leucinostatin analogues (1–4) from Ophiocordyceps spp. and Purpureocillium spp. were determined together with six known leucinostatins [leucinostatins B (5), A (6), B2 (7), A2 (8), F (9), and D (10)]. The structures of the metabolites were established using a combination of analytical methods including HRESIMS and MS/MS experiments, 1D and 2D NMR spectroscopy, chiral HPLC, and advanced Marfey’s analysis of the acid hydrolysate, as well as additional empirical and chemical methods. Compounds 1–10 were evaluated for their biological effects on triple negative breast cancer (TNBC) cells. Leucinostatins 1–10 showed selective cytostatic activities in MDA-MB-453 and SUM185PE cells representing the luminal androgen receptor subtype of TNBC. This selective activity motivated further investigation into the mechanism of action of leucinostatin B (5). The results demonstrate that this peptidic fungal metabolite rapidly inhibits mTORC1 signaling in leucinostatin-sensitive TNBC cell lines, but not in leucinostatin-resistant cells. Leucinostatins have been shown to repress mitochondrial respiration through inhibition of the ATP synthase, and we demonstrated that both the mTORC1 signaling and LAR-selective activities of 5 were recapitulated by oligomycin. Thus, inhibition of the ATP synthase with either leucinostatin B or oligomycin is sufficient to selectively impede mTORC1 signaling and inhibit the growth of LAR-subtype cells.