Correction to "Diving into the Molecular Diversity of Aplysina cavernicola's Exometabolites: Contribution of Bromo-Spiroisoxazoline Alkaloids".

[This corrects the article DOI: 10.1021/acsomega.2c05415.].

Chemical and biological investigation of Indigofera ammoxylum (DC.) Polhill. red and white phenotypes through feature-based molecular networking.

Chemical investigation of ethyl acetate bark extracts of Indigofera ammoxylum red and white phenotypes led to the bio-guided isolation of four previously undescribed flavonoids, named (2S,3R)-3',7-dihydroxy-4',6-dimethoxyflavanol (1), (2S,3R)-6-methoxy-7-hydroxyflavanol (2), 2',3',7-trihydroxy-4',6-dimethoxyisoflavone (7) and 2',5' -dimethoxy-4',5,7-trihydroxyisoflavanone (8), along with 14 known compounds (3-6 and 9-18). The previously undescribed structures were characterized based on NMR, HRESIMS, UV and IR data. Published spectroscopic data were used to deduce the structure of the known compounds. Eleven of the 18 isolated metabolites were evaluated for anti-inflammatory activity and cytotoxic activity against human liver carcinoma cells and human colon and colorectal adenocarcinoma cells. All tested compounds showed an anti-inflammatory activity (IC50 NO < 25 µg/mL), and compounds 2 and 3 were more selective than the positive control dexamethasone. Afromorsin (6) showed promising cytotoxic properties against both cancer cell lines (IC50 18.9 and 11.4 µg/mL). Feature-based molecular networking approach applied to bark and leaves extracts of the two phenotypes allowed to detect bioactive analogues, belonging to the families of flavones, isoflavones, flavanones, flavanols and flavonols, and to explore the chemodiversity of the species. The red and white phenotypes have a similar composition, whereas bark and leaves contain specific chemical entities. Finally, this approach highlighted a cluster of potentially bioactive and undescribed metabolites.

Identification of Antioxidant Metabolites from Five Plants (Calophyllum inophyllum, Gardenia taitensis, Curcuma longa, Cordia subcordata, Ficus prolixa) of the Polynesian Pharmacopoeia and Cosmetopoeia for Skin Care.

Oxidative stress contributes to impairment of skin health, the wound healing process, and pathologies such as psoriasis or skin cancer. Five Polynesian medicinal plants, among the most traditionally used for skin care (pimples, wounds, burns, dermatoses) are studied herein for their antioxidant properties: Calophyllum inophyllum, Gardenia taitensis, Curcuma longa, Cordia subcordata, and Ficus prolixa. Plant extracts were submitted to in vitro bioassays related to antioxidant properties and their bioactive constituents were identified by a metabolomic analytical approach. High performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) analysis was performed leading to the characterization of 61 metabolites. Compounds annotated for F. prolixa and C. subcordata extracts were reported for the first time. Antioxidant properties were evaluated by total phenolic content (TPC), free radical scavenging DPPH (1,1-diphenyl-2-picryl-hydrazyl), and Ferric Reducing Antioxidant Power activity (FRAP) assays. F. prolixa extract was the most active one and showed antioxidant intracellular activity on keratinocytes by Anti Oxydant Power 1 assay. Online HPLC-DPPH allowed the identification of phenolic bioactive compounds such as quercetin-O-rhamnoside, rosmarinic acid, chlorogenic acid, procyanidins, epicatechin, 5-O-caffeoylshikimic acid, and curcumin as being responsible for the scavenging properties of these plant extracts. These results highlight the potential of F. prolixa aerial roots as a source of antioxidants for skin care applications.

Cytotoxic Metabolites from Calophyllum tacamahaca Willd.: Isolation and Detection through Feature-Based Molecular Networking.

Isocaloteysmannic acid (1), a new chromanone, was isolated from the leaf extract of the medicinal species Calophyllum tacamahaca Willd. along with 13 known metabolites belonging to the families of biflavonoids (2), xanthones (3-5, 10), coumarins (6-8) and triterpenes (9, 11-14). The structure of the new compound was characterized based on nuclear magnetic resonance (NMR), high-resolution electrospray mass spectrometry (HRESIMS), ultraviolet (UV) and infrared (IR) data. Its absolute configuration was assigned through electronic circular dichroism (ECD) measurements. Compound (1) showed a moderate cytotoxicity against HepG2 and HT29 cell lines, with IC50 values of 19.65 and 25.68 µg/mL, respectively, according to the Red Dye method. Compounds 7, 8 and 10-13 exhibited a potent cytotoxic activity, with IC50 values ranging from 2.44 to 15.38 µg/mL, against one or both cell lines. A feature-based molecular networking (FBMN) approach led to the detection of a large amount of xanthones in the leaves extract, and particularly analogues of the cytotoxic isolated xanthone pyranojacareubin (10).

Diving into the Molecular Diversity of Aplysina cavernicola's Exometabolites: Contribution of Bromo-Spiroisoxazoline Alkaloids.

Sponges are prolific producers of specialized metabolites with unique structural scaffolds. Their chemical diversity has always inspired natural product chemists working in drug discovery. As part of their metabolic filter-feeding activities, sponges are known to release molecules, possibly including their specialized metabolites. These released "Exo-Metabolites" (EMs) may be considered as new chemical reservoirs that could be collected from the water column while preserving marine biodiversity. The present work aims to determine the proportion and diversity of specialized EMs released by the sponge Aplysina cavernicola (Vacelet 1959). This Mediterranean sponge produces bromo-spiroisoxazoline alkaloids that are widely distributed in the Aplysinidae family. Aquarium experiments were designed to facilitate a continuous concentration of dissolved and diluted metabolites from the seawater around the sponges. Mass Spectrometry (MS)-based metabolomics combined with a dereplication pipeline were performed to investigate the proportion and identity of brominated alkaloids released as EMs. Chemometric analysis revealed that brominated features represented 12% of the total sponge's EM features. Consequently, a total of 13 bromotyrosine alkaloids were reproducibly detected as EMs. The most abundant ones were aerothionin, purealidin L, aerophobin 1, and a new structural congener, herein named aplysine 1. Their structural identity was confirmed by NMR analyses following their isolation. MS-based quantification indicated that these major brominated EMs represented up to 1.0 ± 0.3% w/w of the concentrated seawater extract. This analytical workflow and collected results will serve as a stepping stone to characterize the composition of A. cavernicola's EMs and those released by other sponges through in situ experiments, leading to further evaluate the biological properties of such EMs.

New Metabolites from the Marine Sponge Scopalina hapalia Collected in Mayotte Lagoon.

The biological screening of 44 marine sponge extracts for the research of bioactive molecules, with potential application in the treatment of age-related diseases (cancer and Alzheimer's disease) and skin aging, resulted in the selection of Scopalina hapalia extract for chemical study. As no reports of secondary metabolites of S. hapalia were found in the literature, we undertook this research to further extend current knowledge of Scopalina chemistry. The investigation of this species led to the discovery of four new compounds: two butenolides sinularone J (1) and sinularone K (2), one phospholipid 1-O-octadecyl-2-pentanoyl-sn-glycero-3-phosphocholine (3) and one lysophospholipid 1-O-(3-methoxy-tetradecanoyl)-sn-glycero-3-phosphocholine (4) alongside with known lysophospholipids (5 and 6), alkylglycerols (7-10), epidioxysterols (11 and 12) and diketopiperazines (13 and 14). The structure elucidation of the new metabolites (1-4) was determined by detailed spectroscopic analysis, including 1D and 2D NMR as well as mass spectrometry. Molecular networking was also explored to complement classical investigation and unravel the chemical classes within this species. GNPS analysis provided further information on potential metabolites with additional bioactive natural compounds predicted.

LC-MS Based Phytochemical Profiling towards the Identification of Antioxidant Markers in Some Endemic Aloe Species from Mascarene Islands.

Aloe plant species have been used for centuries in traditional medicine and are reported to be an important source of natural products. However, despite the large number of species within the Aloe genus, only a few have been investigated chemotaxonomically. A Molecular Network approach was used to highlight the different chemical classes characterizing the leaves of five Aloe species: Aloe macra, Aloe vera, Aloe tormentorii, Aloe ferox, and Aloe purpurea. Aloe macra, A. tormentorii, and A. purpurea are endemic from the Mascarene Islands comprising Reunion, Mauritius, and Rodrigues. UHPLC-MS/MS analysis followed by a dereplication process allowed the characterization of 93 metabolites. The newly developed MolNotator algorithm was usedfor molecular networking and allowed a better exploration of the Aloe metabolome chemodiversity. The five species appeared rich in polyphenols (anthracene derivatives, flavonoids, phenolic acids). Therefore, the total phenolic content and antioxidant activity of the five species were evaluated, and a DPPH-On-Line-HPLC assay was used to determine the metabolites responsible for the radical scavenging activity. The use of computational tools allowed a better description of the comparative phytochemical profiling of five Aloe species, which showed differences in their metabolite composition, both qualitative and quantitative. Moreover, the molecular network approach combined with the On-Line-HPLC assay allowed the identification of 9 metabolites responsible for the antioxidant activity. Two of them, aloeresin A and coumaroylaloesin, could be the principal metabolites responsible for the activity. From 374 metabolites calculated by MolNator, 93 could be characterized. Therefore, the Aloe species can be a rich source of new chemical structures that need to be discovered.

Bioassay-guided isolation and UHPLC-DAD-ESI-MS/MS quantification of potential anti-inflammatory phenolic compounds from flowers of Inula montana L.

ETHNOPHARMACOLOGICAL RELEVANCE: Flowers of Inula montana L. (Asteraceae), commonly known as "Arnica de Provence", are used in the traditional medicine of Provence in France with the same indication as Arnica montana, for the relief of bruises, as an anti-inflammatory agent. AIMS OF THE STUDY: The aim of our study is to evaluate its anti-inflammatory properties and to justify its traditional uses. Its potential valorization is evaluated in order to propose Inula montana as an alternative to Arnica montana. MATERIALS AND METHODS: Bio-guided fractionation of ethanolic extract allowed the isolation of compounds responsible of the inhibition of NO production. The fractionation was realized using chromatographic techniques and structure elucidation was conducted by ESI-MS and NMR spectral data. Anti-inflammatory effect of ethanolic extract, different fractions and isolated pure compounds was studied in vitro on immortalized mouse macrophages RAW 264.7. An analytical UHPLC-DAD-ESI-MS/MS method was developed for the identification of these compounds in the herbal drug. This UHPLC-DAD method was validated and was used to compare the phenolic profile and content in plant material from the two collection sites: Bonnieux and Merindol. RESULTS: Eleven compounds were identified by UHPLC-MS. Chlorogenic acid (1), Luteolin (2), Nepetin (3), 3,5-O-Dicaffeoylquinic acid (4), 1,5-O-Dicaffeoylquinic acid (5), Nepitrin (6), Hispiduloside (7) and Jaceosid (8) were isolated and identified by NMR. Compounds 9, 10 and 11 were confirmed to be 6-Hydroxykaempferol 3,7-dimethyl ether, Hispidulin and Chrysosplenol C, respectively by comparing retention times and MS/MS data with those of the authentic substances. Six compounds: 1 and 4-8 are reported for the first time in Inula montana L. Compounds 2-8 showed promising anti-inflammatory activity with the release of NO with IC50 value < 7 µM. The UHPLC-DAD method of quantification of three major bioactive compounds (1, 3 and 5) was validated. CONCLUSION: Flowers extracts and isolated compounds present promising anti-inflammatory activity which provides a scientific basis for the traditional use of Inula montana and may be proposed in the same indications as Arnica montana. The developed and validated simple, accurate and rapid UHPLC method can be used for the quality control of the herbal drug.

New sesquiterpene acid and inositol derivatives from Inula montana L.

A phytochemical investigation of the ethanol extract of leaves and flowers of Inula montana L. led to the isolation of one new sesquiterpene acid called Eldarin (1) and four new inositol derivatives, Myoinositol,1,5-diangelate-4,6-diacetate (2), Myoinositol,1,6-diangelate-4,5-diacetate (3), Myoinositol-1-angelate-4,5-diacetate-6-(2-methylbutirate) (4), Myoinositol-1-angelate-4,5-diacetate-6-isovalerate (5) isolated for the first time, along with eleven known compounds described for the first time in Inula montana, 1ß-Hydroxyarbusculin A (6), Artemorin (7), Santamarin (8), Chrysosplenol C (9), 6-Hydroxykaempferol 3,7-dimethyl ether (10), Reynosin (11), Calenduladiol-3-palmitate (12), Costunolide (13), 4-Hydroxy-3,5-dimethoxybenzenemethanol (14), 9ß-Hydroxycostunolide (15) and Hispidulin (16). Structural elucidation has been carried out by spectral methods, such as 1D and 2D NMR, IR, UV and HR-ESI-MS. These compounds have been tested in vitro for anti-inflammatory and cytotoxic activity on macrophages RAW 264.7. As a result, compounds 2, 3, 7, 13, 14, 15 and 16 showed a release of NO with IC50 value <30µM on macrophages.

Chemical Composition, Antioxidant and Cytotoxic Activities of Roots and Fruits of Berberis libanotica.

Fourteen compounds belonging to different chemical classes were characterized in the roots and fruits extracts from Berberis libanotica, using the same HPLC-DAD-MS method. Thirteen were reported, for the first time, from the fruits whereas the roots contained mostly alkaloids of which 3 out of 5 are reported for the first time. Their structures were established on the basis of MS data as gallic acid (1), chlorogenic acid (2), delphinidin (3), oxyacanthine (4), rutin (5), hyperoside (6), berbamine (7), isoquercitrin (8), quercitrin (9), jatrorrhizine (10), palmatine (11), berberine (12), quercetin (13) and luteolin (14). Extracts containing compounds 4 and 7 showed significant cytotoxicity against the HT29 cell line with an IC50 of 12.2-26.1 µg/mL. Fruits extracts, due mostly to compounds 1 and 2, showed potent antioxidant activities with an EC50 of 0.0025-0.019 mg/mL.