The good phytotoxicity and selectivity against weeds versus tomato or cress make saponin-rich fractions from Agave macroacantha, A. colorata, A. parryi, and A. parrasana attractive candidates as bioherbicides. The saponin contents have only previously been reported for A. macroacantha, and as a consequence, simultaneous dereplication has been performed on saponin-rich fractions from the other plants by mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. This strategy enables the identification of a total of 26 saponins, 14 of which have been described previously and 12 of which are proposed as new saponins. They include isomers and a new sugar chain with a β-d-apiofuranose unit. The method is corroborated by the isolation of eight dereplicated saponins from A. colorata.

Cancer remains a significant global health concern, with mortality rates steadily rising and prompting an urgent search for effective treatments. This study focuses on the medicinal properties of plants from the Phyllanthus genus, specifically Phyllanthus amarus and Phyllanthus niruri, which have shown promise in traditional medicine. Through bioguided fractionation using preparative high-performance liquid chromatography (HPLC), bioactive compounds were isolated and identified using ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-QTOF-MSE) and nuclear magnetic resonance (NMR) spectroscopy. Chemometric analyses such as principal component analysis (PCA) aided in understanding metabolite distribution. Biological assays demonstrated cytotoxic activities of specific fractions against cancer cell lines, notably the PhyN 4n fraction from P. niruri, which induced S-phase cell cycle arrest and apoptosis in HL60 cells. These findings underscore the anticancer potential of Phyllanthus species and lay the groundwork for future drug development efforts. The study\'s integration of advanced analytical techniques, chemometrics, and biological assays provides valuable insights for harnessing natural products in the fight against cancer.

We previously described NMR based fingerprint matching with peptide backbone resonances as a fast and reliable structural dereplication approach for Pseudomonas cyclic lipodepsipeptides (CLiPs). In combination with total synthesis of a small library of configurational CLiP congeners this also allows unambiguous determination of stereochemistry, facilitating structure-activity relationship studies and enabling three-dimensional structure determination. However, the on-resin macrocycle formation in the synthetic workflow brings considerable burden and limits universal applicability. This drawback is here removed altogether by also transforming the native CLiP into a linearized analogue by controlled saponification of the ester bond. This eliminates the need for macrocycle formation, limiting the synthesis effort to linear peptide analogues. NMR fingerprints of such linear peptide analogues display a sufficiently distinctive chemical shift fingerprint to act as effective discriminators. The approach is developed using viscosin group CLiPs and subsequently demonstrated on putisolvin, leading to a structural revision, and tanniamide from Pseudomonas ekonensis COR58, a newly isolated lipododecapeptide that defines a new group characterized by a ten-residue large macrocycle, the largest to date in the Pseudomonas CLiP portfolio. These examples demonstrate the effectiveness of the saponification- enhanced approach that broadens applicability of NMR fingerprint matching for the determination of the stereochemistry of CLiPs.

Narrow-spectrum antibiotics are of great interest given their ability to spare the microbiome and decrease widespread antibiotic resistance compared to broad-spectrum antibiotics. Herein, we screened an in-house library of Actinobacteria strains for selective activity against Acinetobacter baumannii and successfully identified Streptomyces sp. CS-62 as a producer of a natural product with this valuable activity. Analysis of the cultures via high-resolution mass spectrometry and tandem mass spectrometry, followed by comparison with molecules in the Natural Product Atlas and the Global Natural Products Social Molecular Networking platform, suggested a novel natural product. Genome mining analysis initially supported the production of a novel kirromycin derivative. Isolation and structure elucidation via mass spectrometry and Nuclear Magnetic Resonance (NMR) analyses revealed that the active natural product was the known natural product factumycin, exposing omissions and errors in the consulted databases. While public databases are generally very useful for avoiding rediscovery of known molecules, rediscovery remains a problem due to public databases either being incomplete or having errors that result in failed dereplication. Overall, the work describes the ongoing problem of dereplication and the continued need for public database curation.

Women have been found to be at a higher risk of morbidity and mortality from type 2 diabetes mellitus (T2DM) and asthma. α-Glucosidase inhibitors have been used to treat T2DM, and arachidonic acid 15-lipoxygenase (ALOX15) inhibitors have been suggested to be used as treatments for asthma and T2DM. Compounds that inhibit both enzymes may be studied as potential treatments for people with both T2DM and asthma. This study aimed to determine potential anti-diabetic and anti-inflammatory bioactive hits from Coriaria intermedia Matsum. stem and Dracontomelon dao (Blanco) Merr. & Rolfe bark. A bioassay-guided fractionation framework was used to generate bioactive fractions from C. intermedia stem and D. dao bark. Subsequently, dereplication through ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and database searching was performed to putatively identify the components of one bioactive fraction from each plant. Seven compounds were putatively identified from the C. intermedia stem active fraction, and six of these compounds were putatively identified from this plant for the first time. Nine compounds were putatively identified from the D. dao bark active fraction, and seven of these compounds were putatively identified from this plant for the first time. One putative compound from the C. intermedia stem active fraction (corilagin) has been previously reported to have inhibitory activity against both α-glucosidase and 15-lipoxygenase-1. It is suggested that further studies on the potential of corilagin as an anti-diabetic and anti-inflammatory treatment should be pursued based on its several beneficial pharmacological activities and its low reported toxicity.

The discovery of new natural products has become more challenging because of the re-isolation of compounds and the lack of new sources. Microbes dwelling in extreme conditions of high salinity and temperature are huge prospects for interesting natural metabolites. In this study, the endophytic bacteria Bacillus velezensis 7NPB-3B isolated from the halophyte Salicornia brachiata was screened for its biofilm inhibition against methicillin-resistant Staphylococcus aureus (MRSA). The fractionation of the crude extract was guided by bioassay and LC-HRMS-based metabolomics using multivariate analysis. The 37 fractions obtained by high-throughput chromatography were dereplicated using an in-house MS-Excel macro coupled with the Dictionary of Natural Products database. Successive bioactivity-guided separation yielded one novel compound (1), a diketopiperazine (m/z 469.258 [M - H]-) with an attached saturated decanoic acid chain, and four known compounds (2-5). The compounds were identified based on 1D- and 2D-NMR and mass spectrometry. Compounds 1 and 5 exhibited excellent biofilm inhibition properties of >90% against the MRSA pathogen at minimum inhibition concentrations of 25 and 35 µg/mL, respectively. The investigation resulted in the isolation of a novel diketopiperazine from a bacterial endophyte of an untapped plant using an omics approach.

Gymnopilins are long chain oligoisoprenoids produced through the condensation of isoprene units from MEV and MEP biosynthetic pathways. In Gymnopilus, these carotenoid-like molecules are recognized as major compounds in some species. In the present study, oligoisoprenoids derived from gymnopilins were dereplicated from Gymnopilus imperialis, a mushroom-forming basidiomycete, using liquid chromatographic coupled with high-resolution mass spectrometry (tandem LC-HRMS/MS) and GNPS. From the dichloromethane extract (Gym-DCM) of G. imperialis we annotated 3 oligoisoprenoids from the GNPS molecular library spectra and 15 analogs from the curation of the molecular networking. Data from NMR spectroscopic of the extract confirmed the annotation of the metabolites. Based on the literature data suggesting the neurotoxic effect of gymnopilins, we investigated the effects of the administering different doses of gymnopilin extracts (1, 4 or 10 mg/kg) and diazepam (4 mg/kg) on the acquisition of object recognition memory (ORM) in mice. By studying novel object recognition memory (ORM), a type of non-aversive memory. ORM was assessed based on the total time of spontaneous exploration of both objects, the discrimination index (DI), and the frequency of contact with both objects. Our present findings reveal, for the first time, that gymnopilins treatment before training modulates ORM in a dose-dependent manner. It is also suggested that differential effects on memory might be related to differential effects on GABAA receptors but do not exclude its effects in other neurotransmitter systems. Another class of secondary metabolites, alkaloids, might modulate AChR, which is essential for maintaining object recognition memory over time.

This article presents two types of phytochemical data obtained from Brucea javanica (L.) Merr. roots, a medicinal plant belonging to the Simaroubaceae family. The high-resolution LC-MS dataset comprised the chemical profile of dichloromethane extract, which was utilised to annotate 35 chemical constituents. For annotations, the measured spectral data were compared with the in-silico spectral data generated from 920 molecular structures previously reported in Simaroubaceae. Indole alkaloids, quassinoids, aliphatics and lignan were the chemical groups identified in the root extract. The second dataset provides NMR spectra (1H, 13C, COSY, HMQC and HMBC) for the six indole alkaloids previously detected in LC-MS analysis and isolated through centrifugal partition chromatography. The chemical structures of all compounds were confirmed based on NMR data as bruceolline J (compound 7), canthin-6-one-N-oxide (compound 10), bruceolline E (compound 15), 5-methoxycanthin-6-one (compound 16), canthin-6-one (compound 20), and 1‑hydroxy-11-methoxycanthin-6-one (compound 22). This phytochemical data was generated to support an ongoing anti-cancer and anti-dengue study.

Microbial natural products are specialized metabolites that are sources of many bioactive compounds including antibiotics, antifungals, antiparasitics, anticancer agents, and probes of biology. The assembly of libraries of producers of natural products has traditionally been the province of the pharmaceutical industry. This sector has gathered significant historical collections of bacteria and fungi to identify new drug leads with outstanding outcomes-upwards of 60% of drug scaffolds originate from such libraries. Despite this success, the repeated rediscovery of known compounds and the resultant diminishing chemical novelty contributed to a pivot from this source of bioactive compounds toward more tractable synthetic compounds in the drug industry. The advent of advanced mass spectrometry tools, along with rapid whole genome sequencing and in silico identification of biosynthetic gene clusters that encode the machinery necessary for the synthesis of specialized metabolites, offers the opportunity to revisit microbial natural product libraries with renewed vigor. Assembling a suitable library of microbes and extracts for screening requires the investment of resources and the development of methods that have customarily been the proprietary purview of large pharmaceutical companies. Here, we report a perspective on our efforts to assemble a library of natural product-producing microbes and the establishment of methods to extract and fractionate bioactive compounds using resources available to most academic labs. We validate the library and approach through a series of screens for antimicrobial and cytotoxic agents. This work serves as a blueprint for establishing libraries of microbial natural product producers and bioactive extract fractions suitable for screens of bioactive compounds.
UNASSIGNED: Natural products are key to discovery of novel antimicrobial agents: Here, we describe our experience and lessons learned in constructing a microbial natural product and pre-fractionated extract library.

Pterocaulon genus comprises 26 species, half of them have been phytochemical investigations regarding the chemical composition, and coumarins have been considered the chemotaxonomic markers in the genus. Herein Pterocaulon angustifolium DC (Asteraceae), a native plant from Brazil, is investigated for the first time. Twenty-six compounds were isolated from aerial parts of P. angustifolium DC., being 5 triterpenes, 4 phytosterols, 9 flavonoids, 3 phenolic acids, and 5 coumarins. Moreover, a total of 177 compounds were putatively identified using the dereplication technique by UHPLC-HRMS/MS, more than 50% correspond to flavonoids and coumarins. Although 41 different coumarins have already been reported in Pterocaulon genus, 16 were identified for the first time in this study. Crude ethanolic extract and fractions of P. angustifolium were also biologically investigates, and dichloromethane fraction was the most active fraction in the evaluation of antiproliferative, antioxidant, antimicrobial and cholinesterase inhibitory activities.