Quinazolinones, particularly 9-azaglycophymines, and closely related derivatives and precursors were tested in vitro against various breast cancer cell lines representing the major types of breast tumors. Among the 49 compounds tested, azaglycophymine derivative 19 with an electron-withdrawing substituent demonstrated the most significant anti-proliferative effects, with IC50 values of around 4 µM. Extensive cell-based investigations revealed that compound 19 induced caspase-dependent apoptosis in HCC1937 (human TNBC), BT-474 (human HER2+/HR+), and 4T1 (mouse TNBC) cells. In contrast, in MDA-MB-468 (human TNBC) and MCF-7 (human HR+) cells, the cell death was induced via a non-apoptotic pathway. The in vivo efficacy of compound 19 was validated using a syngeneic orthotopic 4T1 model in BALB/c mice, resulting in significant reduction of 4T1 breast tumor growth upon intraperitoneal (i.p.) application of doses of 5 or 20 mg/kg. These findings highlight the potential of compound 19 as a promising scaffold for the development of new therapeutic agents for various types of breast cancer and a first structure-activity insight.

Ajuga turkestanica preparations are used as anti-aging cosmeceuticals and for medicinal purposes. Herein we describe the characterization and quantification of its metabolites in different organs using UHPLC-MS and NMR spectroscopy. A total of 51 compounds belonging to various phytochemical classes (11 flavonoids, 10 ecdysteroids, 9 diterpenes, 6 fatty acids, 5 iridoids, 3 phenylpropanoids, 3 sugars, 2 phenolics, 1 coumarin, 1 triterpene) were annotated and tentatively identified by UHPLC-ESI-QqTOF-MS/MS of methanolic extracts obtained separately from the organs. 1D and 2D NMR spectroscopy independently confirmed the identity of six major compounds. The abundances of these main constituents in flowers, fruits, leaves, roots, seeds, and stems were compared and quantified using 1H NMR. The results showed that 8-O-acetylharpagide, 20-hydroxyecdysone (ecdysterone) and ajugachin B were the most abundant constituents in the species. The two major compounds, 8-O-acetylharpagide and 20-hydroxyecdysone, were chosen as the markers for the quality assessment of A. turkestanica material. The methanolic extract of the aerial parts of A. turkestanica showed no noteworthy anthelmintic (antihelmintic), antifungal, or cytotoxic effect in in vitro assays.

The production of fine-flavor cocoa represents a promising avenue to enhance socioeconomic development in Colombia and Latin America. Premium chocolate is obtained through a post-harvesting process, which relies on semi-standardized techniques. The change in the metabolic profile during cocoa processing considerably impacts flavor and nutraceutical properties of the final product. Understanding this impact considering both volatiles and non-volatile compounds is crucial for process and product re-engineering of cocoa post-harvesting. Consequently, this work studied the metabolic composition of cocoa liquor by untargeted metabolomics and lipidomics. This approach offered a comprehensive view of cocoa biochemistry, considering compounds associated with bioactivity and flavor in cocoa liquor. Their variations were traced back over the cocoa processing (i.e., drying, and roasting), highlighting their impact on flavor development and the nutraceutical properties. These results represent the basis for future studies aimed to re-engineer cocoa post-harvesting considering the variation of key flavor and bioactive compounds over processing.

Treatment of potato plants with the pathogen-associated molecular pattern Pep-13 leads to the activation of more than 1200 genes. One of these, StPIP1_1, encodes a protein of 76 amino acids with sequence homology to PAMP-induced secreted peptides (PIPs) from Arabidopsis thaliana. Expression of StPIP1_1 is also induced in response to infection with Phytophthora infestans, the causal agent of late blight disease. Apoplastic localization of StPIP1_1-mCherry fusion proteins is dependent on the presence of the predicted signal peptide. A synthetic peptide corresponding to the last 13 amino acids of StPIP1_1 elicits the expression of the StPIP1_1 gene itself, as well as that of pathogenesis related genes. The oxidative burst induced by exogenously applied StPIP1_1 peptide in potato leaf disks is dependent on functional StSERK3A/B, suggesting that StPIP1_1 perception occurs via a receptor complex involving the co-receptor StSERK3A/B. Moreover, StPIP1_1 induces expression of FRK1 in Arabidopsis in an RLK7-dependent manner. Expression of an RLK from potato with high sequence homology to AtRLK7 is induced by StPIP1_1, by Pep-13 and in response to infection with P. infestans. These observations are consistent with the hypothesis that, upon secretion, StPIP1_1 acts as an endogenous peptide required for amplification of the defense response.

Tomatoes show diverse phytochemical attributes that contribute to their nutritive and health values. This study comprehensively dissects primary and secondary metabolite profiles of seven tomato varieties. UHPLC-qTOF-MS assisted molecular networking was used to monitor 206 metabolites, 30 of which were first-time to be reported. Flavonoids, as valuable antioxidants, were enriched in light-colored tomatoes (golden sweet, sun gold, and yellow plum) versus high tomatoside A, an antihyperglycemic saponin, in cherry bomb and red plum varieties. UV–Vis analysis revealed similar results with a strong absorbance corresponding to rich phenolic content in light varieties. GC–MS unveiled monosaccharides as the main contributors to samples’ segregation, found abundant in San Marzano tomato accounting for its sweet flavor. Fruits also demonstrated potential antioxidant activities in correlation to their flavonoids and phospholipids. This work provides a complete map of tomatoes’ metabolome heterogeneity for future breeding programs and a comparative approach utilizing different metabolomic platforms for tomato analysis.

M. oleifera known as “miracle tree” is increasingly used in nutraceuticals for the reported health effects and nutritional value of its leaves. This study presents the first metabolome profiling of M. oleifera leaves of African origin using different solvent polarities via HR-UPLC/MS based molecular networking followed by multivariate data analyses for samples classification. 119 Chemicals were characterized in both positive and negative modes belonging to 8 classes viz. phenolic acids, flavonoids, peptides, fatty acids/amides, sulfolipids, glucosinolates and carotenoids. New metabolites i.e., polyphenolics, fatty acids, in addition to a new class of sulfolipids were annotated for the first time in Moringa leaves. In vitro anti-inflammatory and anti-aging bioassays of the leaf extracts were assessed and in correlation to their metabolite profile via multivariate data analyses. Kaempferol, quercetin and apigenin-O/C-glycosides, fatty acyl amides and carotenoids appeared crucial for biological activities and leaves origin discrimination.

With a favored taste and various bioactivities, coffee has been consumed as a daily beverage worldwide. The current study presented a multi-faceted comparative metabolomics approach dissecting commercially available coffee products in the Middle East region for quality assessment and functional food purposes using NMR and GC/MS platforms. NMR metabolites fingerprinting led to identification of 18 metabolites and quantification (qNMR) of six prominent markers for standardization purposes. An increase of β-ethanolamine (MEA) reported for the first time, 5-(hydroxymethyl) furfural (5-HMF), concurrent with a reduction in chlorogenic acid, kahweol, and sucrose levels post roasting as revealed using multivariate data analyses (MVA). The diterpenes kahweol and cafestol were identified in green and roasted Coffea arabica, while 16-O-methyl cafestol in roasted C. robusta. Moreover, GC/MS identified a total of 143 metabolites belonging to 15 different chemical classes, with fructose found enriched in green C. robusta versus fatty acids abundance, i.e., palmitic and stearic acids in C. arabica confirming NMR results. These potential results aided to identify novel quality control attributes, i.e., ethanolamine, for coffee in the Middle East region and have yet to be confirmed in other coffee specimens.

The impact of cocoa lipid content on chocolate quality has been extensively described. Nevertheless, few studies have elucidated the cocoa lipid composition and their bioactive properties, focusing only on specific lipids. In the present study the lipidome of fine-flavor cocoa fermentation was analyzed using LC-MS-QTOF and a Machine Learning model to assess potential bioactivity was developed. Our results revealed that the cocoa lipidome, comprised mainly of fatty acyls and glycerophospholipids, remains stable during fine-flavor cocoa fermentations. Also, several Machine Learning algorithms were trained to explore potential biological activity among the identified lipids. We found that K-Nearest Neighbors had the best performance. This model was used to classify the identified lipids as bioactive or non-bioactive, nominating 28 molecules as potential bioactive lipids. None of these compounds have been previously reported as bioactive. Our work is the first untargeted lipidomic study and systematic effort to investigate potential bioactivity in fine-flavor cocoa lipids.

Saffron is a spice revered for its unique flavor and health attributes often subjected to fraudulence. In this study, molecular networking as a visualization tool for UPLC/MS dataset of saffron and its common substitutes i.e. safflower and calendula (n = 21) was employed for determining genuineness of saffron and detecting its common substitutes i.e. safflower and calendula. Saffron was abundant in flavonol-O-glycosides and crocetin esters versus richness of flavanones/chalcones glycosides in safflower and cinnamates/terpenes in calendula. OPLS-DA identified differences in UPLC/MS profiles of different saffron accessions where oxo-hydroxy-undecenoic acid-O-hexoside was posed as saffron authentication marker and aided in discrimination between Spanish saffron of high quality from its inferior grade i.e. Iranian saffron along with crocetin di-O-gentiobiosyl ester and kaempferol-O-sophoroside. Kaempferol-O-neohesperidoside and N,N,N,-p-coumaroyl spermidine were characteristic safflower metabolites, whereas, calendulaglycoside C and di-O-caffeoyl quinic acid were unique to calendula. UV/VIS fingerprint spectral regions of picrocrocin (230–260 nm) and crocin derivatives (400–470 nm) were posed as being discriminatory of saffron authenticity and suggestive it can replace UPLC/MS in saffrom quality determination.

Chronic diseases affecting the central nervous system (CNS) like Alzheimer’s or Parkinson’s disease typically develop with advanced chronological age. Yet, aging at the metabolic level has been explored only sporadically in humans using biofluids in close proximity to the CNS such as the cerebrospinal fluid (CSF). We have used an untargeted liquid chromatography high-resolution mass spectrometry (LC-HRMS) based metabolomics approach to measure the levels of metabolites in the CSF of non-neurological control subjects in the age of 20 up to 74. Using a random forest-based feature selection strategy, we extracted 69 features that were strongly related to age (page