Comparative metabolite analysis of Piper sarmentosum organs approached by LC-MS-based metabolic profiling.

Piper sarmentosum Roxb. (Piperaceae) is a traditional medicinal and food plant widely distributed in the tropical and subtropical regions of Asia, offering both health and culinary benefits. In this study the secondary metabolites in different organs of P. sarmentosum were identified and their relative abundances were characterized. The metabolic profiles of leaves, roots, stems and fruits were comprehensively investigated by liquid chromatography high-resolution mass spectrometry (LC-HR-MS) and the data subsequently analyzed using multivariate statistical methods. Manual interpretation of the tandem mass spectrometric (MS/MS) fragmentation patterns revealed the presence of 154 tentatively identified metabolites, mostly represented by alkaloids and flavonoids. Principle component analysis and hierarchical clustering indicated the predominant occurrence of flavonoids, lignans and phenyl propanoids in leaves, aporphines in stems, piperamides in fruits and lignan-amides in roots. Overall, this study provides extensive data on the metabolite composition of P. sarmentosum, supplying useful information for bioactive compounds discovery and patterns of their preferential biosynthesis or storage in specific organs. This can be used to optimize production and harvesting as well as to maximize the plant's economic value as herbal medicine or in food applications.

Improved access to potent anticancer tubulysins and linker-functionalized payloads via an all-on-resin.

Tubulysins are among the most recent antimitotic compounds to enter into antibody/peptide-drug conjugate (ADC/PDC) development. Thus far, the design of the most promising tubulysin payloads relied on simplifying their structures, e.g., by using small tertiary amide N-substituents (Me, Et, Pr) on tubuvaline residue. Cumbersome solution-phase approaches are typically used for both syntheses and functionalization with cleavable linkers. p-Aminobenzyl quaternary ammonium (PABQ) linkers were a remarkable advancement for targeted delivery, but the procedures to incorporate them into tubulysins are only of moderate efficiency. Here we describe a novel all-on-resin strategy permitting a loss-free resin linkage and an improved access to super potent tubulysin analogs showing close resemblance to the natural compounds. For the first time, a protocol enables the integration of on-resin tubulysin derivatization with, e.g., a maleimido-Val-Cit-PABQ linker, which is a notable progress for the payload-PABQ-linker technology. The strategy also allows tubulysin diversification of the internal amide N-substituent, thus enabling to screen a tubulysin library for the discovery of new potent analogs. This work provides ADC/PDC developers with new tools for both rapid access to new derivatives and easier linker-attachment and functionalization.

Assessment of metabolome diversity in black and white pepper in response to autoclaving using MS- and NMR-based metabolomics and in relation to its remote and direct antimicrobial effects against food-borne pathogens.

Piper nigrum L. (black and white peppercorn) is one of the most common culinary spices used worldwide. The current study aims to dissect pepper metabolome using 1H-NMR targeting of its major primary and secondary metabolites. Eighteen metabolites were identified with piperine detected in black and white pepper at 20.2 and 23.9 µg mg-1, respectively. Aroma profiling using HS-SPME coupled to GC-MS analysis and in the context of autoclave treatment led to the detection of a total of 52 volatiles with an abundance of ß-caryophyllene at 82% and 59% in black and white pepper, respectively. Autoclaving of black and white pepper revealed improvement of pepper aroma as manifested by an increase in oxygenated compounds' level. In vitro remote antimicrobial activity against food-borne Gram-positive and Gram-negative bacteria revealed the highest activity against P. aeruginosa (VP-MIC 16.4 and 12.9 mg mL-1) and a direct effect against Enterobacter cloacae at ca. 11.6 mg mL-1 for both white and black pepper.

Enzymatic one-step synthesis of natural 2-pyrones and new-to-nature derivatives from coenzyme A esters.

The 2-pyrone moiety is present in a wide range of structurally diverse natural products with various biological activities. The plant biosynthetic routes towards these compounds mainly depend on the activity of either type III polyketide synthase-like 2-pyrone synthases or hydroxylating 2-oxoglutarate dependent dioxygenases. In the present study, the substrate specificity of these enzymes is investigated by a systematic screening using both natural and artificial substrates with the aims of efficiently forming (new) products and understanding the underlying catalytic mechanisms. In this framework, we focused on the in vitro functional characterization of a 2-pyrone synthase Gh2PS2 from Gerbera x hybrida and two dioxygenases AtF6'H1 and AtF6'H2 from Arabidopsis thaliana using a set of twenty aromatic and aliphatic CoA esters as substrates. UHPLC-ESI-HRMSn based analyses of reaction intermediates and products revealed a broad substrate specificity of the enzymes, enabling the facile "green" synthesis of this important class of natural products and derivatives in a one-step/one-pot reaction in aqueous environment without the need for halogenated or metal reagents and protective groups. Using protein modeling and substrate docking we identified amino acid residues that seem to be important for the observed product scope.

A multiplex approach of MS, 1D-, and 2D-NMR metabolomics in plant ontogeny: A case study on Clusia minor L. organs (leaf, flower, fruit, and seed).

INTRODUCTION: The genus Clusia L. is mostly recognised for the production of prenylated benzophenones and tocotrienol derivatives. OBJECTIVES: The objective of this study was to map metabolome variation within Clusia minor organs at different developmental stages. MATERIAL AND METHODS: In total 15 organs/stages (leaf, flower, fruit, and seed) were analysed by UPLC-MS and 1H- and heteronuclear multiple-bond correlation (HMBC)-NMR-based metabolomics. RESULTS: This work led to the assignment of 46 metabolites, belonging to organic acids(1), sugars(2) phenolic acids(1), flavonoids(3) prenylated xanthones(1) benzophenones(4) and tocotrienols(2). Multivariate data analyses explained the variability and classification of samples, highlighting chemical markers that discriminate each organ/stage. Leaves were found to be rich in 5-hydroxy-8-methyltocotrienol (8.5 µg/mg f.w.), while flowers were abundant in the polyprenylated benzophenone nemorosone with maximum level detected in the fully mature flower bud (43 µg/mg f.w.). Nemorosone and 5-hydroxy tocotrienoloic acid were isolated from FL6 for full structural characterisation. This is the first report of the NMR assignments of 5-hydroxy tocotrienoloic acid, and its maximum level was detected in the mature fruit at 50 µg/mg f.w. Seeds as typical storage organ were rich in sugars and omega-6 fatty acids. CONCLUSION: To the best of our knowledge, this is the first report on a comparative 1D-/2D-NMR approach to assess compositional differences in ontogeny studies compared with LC-MS exemplified by Clusia organs. Results derived from this study provide better understanding of the stages at which maximal production of natural compounds occur and elucidate in which developmental stages the enzymes responsible for the production of such metabolites are preferentially expressed.

Diversification of a Novel α-Galactosyl Ceramide Hotspot Boosts the Adjuvant Properties in Parenteral and Mucosal Vaccines.

The development of potent adjuvants is an important step for improving the performance of subunit vaccines. CD1d agonists, such as the prototypical α-galactosyl ceramide (α-GalCer), are of special interest due to their ability to activate iNKT cells and trigger rapid dendritic cell maturation and B-cell activation. Herein, we introduce a novel derivatization hotspot at the α-GalCer skeleton, namely the N-substituent at the amide bond. The multicomponent diversification of this previously unexplored glycolipid chemotype space permitted the introduction of a variety of extra functionalities that can either potentiate the adjuvant properties or serve as handles for further conjugation to antigens toward the development of self-adjuvanting vaccines. This strategy led to the discovery of compounds eliciting enhanced antigen-specific T cell stimulation and a higher antibody response when delivered by either the parenteral or the mucosal route, as compared to a known potent CD1d agonist. Notably, various functionalized α-GalCer analogues showed a more potent adjuvant effect after intranasal immunization than a PEGylated α-GalCer analogue previously optimized for this purpose. Ultimately, this work could open multiple avenues of opportunity for the use of mucosal vaccines against microbial infections.

Indonesian marine and its medicinal contribution.

The archipelagic country of Indonesia is populated by the densest marine biodiversity in the world which has created strong global interest and is valued by both Indigenous and European settlements for different purposes. Nearly 1000 chemicals have been extracted and identified. In this review, a systematic data curation was employed to collate bioprospecting related manuscripts providing a comprehensive directory based on publications from 1988 to 2022. Findings with significant pharmacological activities are further discussed through a scoping data collection. This review discusses macroorganisms (Sponges, Ascidian, Gorgonians, Algae, Mangrove) and microorganism (Bacteria and Fungi) and highlights significant discoveries, including a potent microtubule stabilizer laulimalide from Hyattella sp., a prospective doxorubicin complement papuamine alkaloid from Neopetrosia cf exigua, potent antiplasmodial manzamine A from Acanthostrongylophora ingens, the highly potent anti trypanosomal manadoperoxide B from Plakortis cfr. Simplex, mRNA translation disrupter hippuristanol from Briareum sp, and the anti-HIV-1 (+)-8-hydroxymanzamine A isolated from Acanthostrongylophora sp. Further, some potent antibacterial extracts were also found from a limited biomass of bacteria cultures. Although there are currently no examples of commercial drugs from the Indonesian marine environment, this review shows the molecular diversity present and with the known understudied biodiversity, reveals great promise for future studies and outcomes.

Comparison of Balanites aegyptiaca parts: metabolome providing insights into plant health benefits and valorization purposes as analyzed using multiplex GC-MS, LC-MS, NMR-based metabolomics, and molecular networking.

Balanites aegyptiaca (L.) Delile (Zygophyllaceae), also known as the desert date, is an edible fruit-producing tree popular for its nutritional and several health benefits. In this study, multi-targeted comparative metabolic profiling and fingerprinting approaches were conducted for the assessment of the nutrient primary and secondary metabolite heterogeneity in different parts, such as leaves, stems, seeds, unripe, and ripe fruits of B. aegyptiaca using nuclear magnetic resonance (NMR), ultra-performance liquid chromatography (UPLC-MS), and gas chromatography mass-spectrometry (GC-MS) based metabolomics coupled to multivariate analyses and in relation to its cytotoxic activities. NMR-based metabolomic study identified and quantified 15 major primary and secondary metabolites belonging to alkaloids, saponins, flavonoids, sugars, and amino and fatty acids. Principal component analysis (PCA) of the NMR dataset revealed α-glucose, sucrose, and isorhamnetin as markers for fruit and stem and unsaturated fatty acids for predominated seeds. Orthogonal projections to latent structure discriminant analysis (OPLS-DA) revealed trigonelline as a major distinctive metabolite in the immature fruit and isorhamnetin as a major distinct marker in the mature fruit. UPLC-MS/MS analysis using feature-based molecular networks revealed diverse chemical classes viz. steroidal saponins, N-containing metabolites, phenolics, fatty acids, and lipids as the constitutive metabolome in Balanites. Gas chromatography-mass spectroscopy (GC-MS) profiling of primary metabolites led to the detection of 135 peaks belonging to sugars, fatty acids/esters, amino acids, nitrogenous, and organic acids. Monosaccharides were detected at much higher levels in ripe fruit and disaccharides in predominate unripe fruits, whereas B. aegyptiaca vegetative parts (leaves and stem) were rich in amino acids and fatty acids. The antidiabetic compounds, viz, nicotinic acid, and trigonelline, were detected in all parts especially unripe fruit in addition to the sugar alcohol d-pinitol for the first time providing novel evidence for B. aegyptiaca use in diabetes. In vitro cytotoxic activity revealed the potential efficacy of immature fruit and seeds as cytotoxic agents against human prostate cancer (PC3) and human colorectal cancer (HCT-116) cell lines. Collectively, such detailed profiling of parts provides novel evidence for B. aegyptiaca medicinal uses.

Prenylated Isoflavanones with Antimicrobial Potential from the Root Bark of Dalbergia melanoxylon.

Dalbergia melanoxylon Guill. & Perr (Fabaceae) is widely utilized in the traditional medicine of East Africa, showing effects against a variety of ailments including microbial infections. Phytochemical investigation of the root bark led to the isolation of six previously undescribed prenylated isoflavanones together with eight known secondary metabolites comprising isoflavanoids, neoflavones and an alkyl hydroxylcinnamate. Structures were elucidated based on HR-ESI-MS, 1- and 2-D NMR and ECD spectra. The crude extract and the isolated compounds of D. melanoxylon were tested for their antibacterial, antifungal, anthelmintic and cytotoxic properties, applying established model organisms non-pathogenic to humans. The crude extract exhibited significant antibacterial activity against Gram-positive Bacillus subtilis (97% inhibition at 50 µg/mL) and antifungal activity against the phytopathogens Phytophthora infestans, Botrytis cinerea and Septoria tritici (96, 89 and 73% at 125 µg/mL, respectively). Among the pure compounds tested, kenusanone H and (3R)-tomentosanol B exhibited, in a panel of partially human pathogenic bacteria and fungi, promising antibacterial activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and Mycobacterium showing MIC values between 0.8 and 6.2 µg/mL. The observed biological effects support the traditional use of D. melanoxylon and warrant detailed investigations of its prenylated isoflavanones as antibacterial lead compounds.

Advancing Multicomponent Strategies to Macrobicyclic Peptides.

Macrocyclization of peptides is typically used to fix specific bioactive conformations and improve their pharmacological properties. Recently, macrobicyclic peptides have received special attention owing to their capacity to mimic protein structures or be key components of peptide-drug conjugates. Here, we describe the development of novel synthetic strategies for two distinctive types of peptide macrobicycles. A multicomponent macrocyclo-dimerization approach is introduced for the production of interconnected ß-turns, allowing two macrocyclic rings to be formed and dimerized in one pot. Also, an on-resin double stapling strategy is described for the assembly of lactam-bridged macrobicycles with stable tertiary folds.

Metabolomics characterizes early metabolic changes and markers of tolerant Eucalyptus ssp. clones against drought stress.

EUCALYPTUS: L'Hér. (Myrtaceae) is one of the economically most important and widely cultivated trees for wood crop purposes worldwide. Climatic changes together with the constant need to expand plantations to areas that do not always provide optimal conditions for plant growth highlight the need to assess the impact of abiotic stresses on eucalypt trees. We aimed to unveil the drought effect on the leaf metabolome of commercial clones with differential phenotypic response to this stress. For this, seedlings of 13 clones were grown at well-watered (WW) and water-deficit (WD) conditions and their leaf extracts were subjected to comparative analysis using ultra-high performance liquid chromatography coupled to mass spectrometry (UPLC-MS) and nuclear magnetic resonance spectroscopy (NMR). UPLC-MS and NMR analyses led to the annotation of over 100 molecular features of classes such as cyclitols, phenolics, flavonoids, formylated phloroglucinol compounds (FPCs) and fatty acids. Multivariate data analysis was employed for specimens' classifications and markers identification from both platforms. The results obtained in this work allowed us to classify clones differing in drought tolerance. Classification models were validated using an extra subset of samples. Tolerant plants exposed to water deficit accumulated arginine, gallic acid derivatives, caffeic acid and tannins at higher levels. In contrast, stressed drought-sensitive clones were characterised by a significant reduction in glucose, inositol and shikimic acid levels. These changes in contrasting drought response eucalypt pave ways for differential outcomes of tolerant and susceptible phenotypes. Under optimal growth conditions, all clones were rich in FPCs. These results can be used for early screening of tolerant clones and to improve our understanding of the role of these biomarkers in Eucalyptus tolerance to drought stress.

Challenging Structure Elucidation of Lumnitzeralactone, an Ellagic Acid Derivative from the Mangrove Lumnitzera racemosa.

The previously undescribed natural product lumnitzeralactone (1), which represents a derivative of ellagic acid, was isolated from the anti-bacterial extract of the Indonesian mangrove species Lumnitzera racemosa Willd. The structure of lumnitzeralactone (1), a proton-deficient and highly challenging condensed aromatic ring system, was unambiguously elucidated by extensive spectroscopic analyses involving high-resolution mass spectrometry (HRMS), 1D 1H and 13C nuclear magnetic resonance spectroscopy (NMR), and 2D NMR (including 1,1-ADEQUATE and 1,n-ADEQUATE). Determination of the structure was supported by computer-assisted structure elucidation (CASE system applying ACD-SE), density functional theory (DFT) calculations, and a two-step chemical synthesis. Possible biosynthetic pathways involving mangrove-associated fungi have been suggested.

Unveiling metabolome heterogeneity and new chemicals in 7 tomato varieties via multiplex approach of UHPLC-MS/MS, GC-MS, and UV-Vis in relation to antioxidant effects as analyzed using molecular networking and chemometrics.

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.

Molecular Modes of Action of an Aqueous Nerium oleander Extract in Cancer Cells In Vitro and In Vivo.

Cancer drug resistance remains a major obstacle in clinical oncology. As most anticancer drugs are of natural origin, we investigated the anticancer potential of a standardized cold-water leaf extract from Nerium oleander L., termed Breastin. The phytochemical characterization by nuclear magnetic resonance spectroscopy (NMR) and low- and high-resolution mass spectrometry revealed several monoglycosidic cardenolides as major constituents (adynerin, neritaloside, odoroside A, odoroside H, oleandrin, and vanderoside). Breastin inhibited the growth of 14 cell lines from hematopoietic tumors and 5 of 6 carcinomas. Remarkably, the cellular responsiveness of odoroside H and neritaloside was not correlated with all other classical drug resistance mechanisms, i.e., ATP-binding cassette transporters (ABCB1, ABCB5, ABCC1, ABCG2), oncogenes (EGFR, RAS), tumor suppressors (TP53, WT1), and others (GSTP1, HSP90, proliferation rate), in 59 tumor cell lines of the National Cancer Institute (NCI, USA), indicating that Breastin may indeed bypass drug resistance. COMPARE analyses with 153 anticancer agents in 74 tumor cell lines of the Oncotest panel revealed frequent correlations of Breastin with mitosis-inhibiting drugs. Using tubulin-GFP-transfected U2OS cells and confocal microscopy, it was found that the microtubule-disturbing effect of Breastin was comparable to that of the tubulin-depolymerizing drug paclitaxel. This result was verified by a tubulin polymerization assay in vitro and molecular docking in silico. Proteome profiling of 3171 proteins in the NCI panel revealed protein subsets whose expression significantly correlated with cellular responsiveness to odoroside H and neritaloside, indicating that protein expression profiles can be identified to predict the sensitivity or resistance of tumor cells to Breastin constituents. Breastin moderately inhibited breast cancer xenograft tumors in vivo. Remarkably, in contrast to what was observed with paclitaxel monotherapy, the combination of paclitaxel and Breastin prevented tumor relapse, indicating Breastin's potential for drug combination regimens.

Identification and Characterization of Three New Antimicrobial Peptides from the Marine Mollusk Nerita versicolor (Gmelin, 1791).

Mollusks have been widely investigated for antimicrobial peptides because their humoral defense against pathogens is mainly based on these small biomolecules. In this report, we describe the identification of three novel antimicrobial peptides from the marine mollusk Nerita versicolor. A pool of N. versicolor peptides was analyzed with nanoLC-ESI-MS-MS technology, and three potential antimicrobial peptides (Nv-p1, Nv-p2 and Nv-p3) were identified with bioinformatical predictions and selected for chemical synthesis and evaluation of their biological activity. Database searches showed that two of them show partial identity to histone H4 peptide fragments from other invertebrate species. Structural predictions revealed that they all adopt a random coil structure even when placed near a lipid bilayer patch. Nv-p1, Nv-p2 and Nv-p3 exhibited activity against Pseudomonas aeruginosa. The most active peptide was Nv-p3 with an inhibitory activity starting at 1.5 µg/mL in the radial diffusion assays. The peptides were ineffective against Klebsiella pneumoniae, Listeria monocytogenes and Mycobacterium tuberculosis. On the other hand, these peptides demonstrated effective antibiofilm action against Candida albicans, Candida parapsilosis and Candida auris but not against the planktonic cells. None of the peptides had significant toxicity on primary human macrophages and fetal lung fibroblasts at effective antimicrobial concentrations. Our results indicate that N. versicolor-derived peptides represent new AMP sequences and have the potential to be optimized and developed into antibiotic alternatives against bacterial and fungal infections.

Characterization and Bioactive Potential of Secondary Metabolites Isolated from Piper sarmentosum Roxb.

Piper sarmentosum Roxb. (Piperaceae) is a traditional medicinal plant in South-East Asian countries. The chemical investigation of leaves from this species resulted in the isolation of three previously not described compounds, namely 4″-(3-hydroxy-3-methylglutaroyl)-2″-ß-D-glucopyranosyl vitexin (1), kadukoside (2), and 6-O-trans-p-coumaroyl-D-glucono-1,4-lactone (3), together with 31 known compounds. Of these known compounds, 21 compounds were isolated for the first time from P. sarmentosum. The structures were established by 1D and 2D NMR techniques and HR-ESI-MS analyses. The compounds were evaluated for their anthelmintic (Caenorhabditis elegans), antifungal (Botrytis cinerea, Septoria tritici and Phytophthora infestans), antibacterial (Aliivibrio fischeri) and cytotoxic (PC-3 and HT-29 human cancer cells lines) activities. Methyl-3-(4-methoxyphenyl)propionate (8), isoasarone (12), and trans-asarone (15) demonstrated anthelmintic activity with IC50 values between 0.9 and 2.04 mM. Kadukoside (2) was most active against S. tritici with IC50 at 5.0 µM and also induced 94% inhibition of P. infestans growth at 125 µM. Trans-asarone (15), piperolactam A (23), and dehydroformouregine (24) displayed a dose-dependent effect against B. cinerea from 1.5 to 125 µM up to more than 80% inhibition. Paprazine (19), cepharadione A (21) and piperolactam A (23) inhibited bacterial growth by more than 85% at 100 µM. Only mild cytotoxic effects were observed.

Lehmanniaside, a new cycloartane triterpene glycoside from Astragalus lehmannianus.

Chemical investigation of the aerial parts of Astragalus lehmannianus Bunge (Leguminosae) led to the isolation and identification of a new cycloartane triterpene glycoside - lehmanniaside (2'-O-acetyl-3-ß-O-D-xylopyranosyl-3ß,6α,16ß,24α-tetrahydroxy-20,25-epoxycycloartane). Its structure was elucidated by means of spectroscopic analysis (HR-MS, 1D and 2D NMR). Bioassays showed that lehmanniaside exhibits weak anthelmintic, antifungal, and cytotoxic activities.

A New Ceramide from Cissus Aralioides Baker (Vitaceae) and its Antimicrobial Activity.

Purification through repeated column chromatography over silica gel and Sephadex LH-20 of the ethanol extract of the stems of Cissus aralioides (Baker) Planch. resulted in the isolation of a new ceramide, aralioidamide A (1), along with five known compounds (2-6). Their structures were determined by the extensive analyses of their spectroscopic (1D and 2D NMR) and spectrometric data, and comparison with those reported in the literature. Aralioidamide A (1) displayed weak antibacterial activity (MIC=256 µg/mL) against Bacillus subtilis, Staphylococcus aureus and Shigella flexneri and was inactive (MIC>256 µg/mL) against the tested fungi.

Bichromonol, a dimeric coumarin with anti-HIV activity from the stem bark of Hypericum roeperianum.

Infectious diseases caused by viruses like HIV and SARS-COV-2 (COVID-19) pose serious public health threats. In search for new antiviral small molecules from chemically underexplored Hypericum species, a previously undescribed atropisomeric C8-C8' linked dimeric coumarin named bichromonol (1) was isolated from the stem bark of Hypericum roeperianum. The structure was elucidated by MS data and NMR spectroscopy. The absolute configuration at the biaryl axis was determined by comparing the experimental ECD spectrum with those calculated for the respective atropisomers. Bichromonol was tested in cell-based assays for cytotoxicity against MT-4 (CC50 = 54 µM) cells and anti-HIV activity in infected MT-4 cells. It exhibits significant activity at EC50 = 6.6-12.0 µM against HIV-1 wild type and its clinically relevant mutant strains. Especially, against the resistant variants A17 and EFVR, bichromonol is more effective than the commercial drug nevirapine and might thus have potential to serve as a new anti-HIV lead.

Dissection of Moringa oleifera leaf metabolome in context of its different extracts, origin and in relationship to its biological effects as analysed using molecular networking and chemometrics.

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.