Residual levels of pesticides in filet green beans from Souss-Massa, Morocco.

A total of 30 samples of filet green beans (Phaseolus vulgaris) from various popular markets in the Souss-Massa region (Morocco) were analyzed during 2021 for the presence of pesticide residues. We performed a QuEChERS extraction (Quick, Easy, Cheap, Effective, Rugged, and Safe) combined with Liquid Chromatography-Mass Spectrometry (LC-MS/MS) and Gas Chromatography-Mass Spectrometry (GC-MS/MS). The method was validated in accordance with SANTE 11312/2021 guidelines. The results of this survey indicated that 8 out of 30 green bean samples are positives (0.015 to 0.112 mg/kg). Azoxystrobin was the most frequently detected pesticide, occurring in 5 samples. For authorized pesticides, none of the samples exceeded the European Maximum residue level (EU MRL) in green beans, but residue of fipronil-unauthorized substance was detected in one sample at 0.027 mg/kg. Hence, it is important to increase inspections for locally marketed fresh green beans and align agricultural practices with regulatory requirements.

Photoprotective potential of Passiflora cincinnata Mast. (Passifloraceae) hydro-alcoholic extracts.

Passiflora cincinnata is a Passifloraceae typical of the Caatinga, a biome unique to Brazil. It has various pharmacological properties associated with its high flavonoid content. Vitexin, isovitexin, orientin, isoorientin and derivatives are the main chemical and pharmacological markers for this plant. Although flavonoids enriched-extracts have been widely applied in phytocosmetics, especially in sunscreen formulations, the use of P. cincinnata as a photoprotective ingredient remains unexplored. Different hydro-alcoholic extracts were prepared and their antioxidant and photoprotective activities were evaluated by in vitro assays. The most promising extract (Pc-1) was analyzed by HPLC-DAD-ESI-MS/MS. Nine flavonoids were identified as major compounds: isovitexin-7-O-glucoside, isoorientin-2"O-hexoside, orientin, isoorientin, isovitexin-2"-O-glucoside, isovitexin-6"-O-glucoside, isoscoparin and isoquercitrin. Finally, Pc-1 (5 and 10%, v/v) was incorporated into gel formulations, alone or combined to commercial chemical filters (benzophenone-3 and octyl methoxycinnamate). Formulations containing Pc-1 showed high SPFspectrophotometric values. When combined to commercial filters, Pc-1 (5%) potentiated their photoprotective efficacy (p<0.05). A physicochemical characterization indicated no incompatibility or signs of instability after extract incorporation. Altogether, these findings encourage the use of Pc-1 as a photoprotective ingredient or co-adjuvant in sunscreens formulations.

Valorization of Dairy and Fruit/Berry Industry By-Products to Sustainable Marinades for Broilers' Wooden Breast Meat Quality Improvement.

The study aims to improve the quality of wooden breast meat (WBM) via the use of newly developed marinades based on selected strains of lactic acid bacteria (LAB) in combination with the by-products of the dairy and fruit/berry industries. Six distinct marinades were produced based on milk permeate (MP) fermented with Lacticaseibacillus casei (Lc) and Liquorilactobacillus uvarum (Lu) with the addition of apple (ApBp) and blackcurrant (BcBp) processing by-products. The microbiological and acidity parameters of the fermented marinades were evaluated. The effects of marinades on the microbiological, technical, and physicochemical properties of meat were assessed following 24 and 48 h of WBM treatment. It was established that LAB viable counts in marinades were higher than 7.00 log10 colony-forming units (CFU)/mL and, after 48 h of marination, enterobacteria and molds/yeasts in WBM were absent. Marinated (24 and 48 h) WBM showed lower dry-matter and protein content, as well as water holding capacity, and exhibited higher drip loss (by 8.76%) and cooking loss (by 12.3%) in comparison with controls. After WBM treatment, biogenic amines decreased; besides, the absence of spermidine and phenylethylamine was observed in meat marinated for 48 h with a marinade prepared with Lu. Overall, this study highlights the potential advantages of the developed sustainable marinades in enhancing the safety and quality attributes of WBM.

Contribution to the characterization of the seed endophyte microbiome of Argania spinosa across geographical locations in Central Morocco using metagenomic approaches.

Microbial endophytes are microorganisms that live inside plants, and some of them play important yet understudied roles in plant health, growth, and adaptation to environmental conditions. Their diversity within plants has traditionally been underestimated due to the limitations of culture-dependent techniques. Metagenomic profiling provides a culture-independent approach to characterize entire microbial communities. The argan tree (Argania spinosa) is ecologically and economically important in Morocco, yet its seed endophyte microbiome remains unexplored. This study aimed to compare the bacterial and fungal endophyte communities associated with argan seeds collected from six sites across Morocco using Illumina MiSeq sequencing of the 16S rRNA gene and ITS regions, respectively. Bacterial DNA was extracted from surface-sterilized seeds and amplified using universal primers, while fungal DNA was isolated directly from seeds. Bioinformatics analysis of sequencing data identified taxonomic profiles at the phylum to genus levels. The results indicated that bacterial communities were dominated by the genus Rhodoligotrophos, while fungal communities exhibited varying degrees of dominance between Ascomycota and Basidiomycota depending on site, with Penicillium being the most abundant overall. Distinct site-specific profiles were observed, with Pseudomonas, Bacillus, and Aspergillus present across multiple locations. Alpha diversity indices revealed variation in endophyte richness between seed sources. In conclusion, this first exploration of the argan seed endophyte microbiome demonstrated environmental influence on community structure. While facing limitations due to small sample sizes and lack of ecological metadata, it provides a foundation for future mechanistic investigations into how specific endophyte-host interactions shape argan adaptation across Morocco's diverse landscapes.

A Comprehensive Review on Cannabis sativa Ethnobotany, Phytochemistry, Molecular Docking and Biological Activities.

For more than a century, Cannabis was considered a narcotic and has been banned by lawmakers all over the world. In recent years, interest in this plant has increased due to its therapeutic potential, in addition to a very interesting chemical composition, characterized by the presence of an atypical family of molecules known as phytocannabinoids. With this emerging interest, it is very important to take stock of what research has been conducted so far on the chemistry and biology of Cannabis sativa. The aim of this review is to describe the traditional uses, chemical composition and biological activities of different parts of this plant, as well as the molecular docking studies. Information was collected from electronic databases, namely SciFinder, ScienceDirect, PubMed and Web of Science. Cannabis is mainly popular for its recreational use, but it is also traditionally used as remedy for the treatment of several diseases, including diabetes, digestive, circulatory, genital, nervous, urinary, skin and respiratory diseases. These biological proprieties are mainly due to the presence of bioactive metabolites represented by more than 550 different molecules. Molecular docking simulations proved the presence of affinities between Cannabis compounds and several enzymes responsible for anti-inflammatory, antidiabetic, antiepileptic and anticancer activities. Several biological activities have been evaluated on the metabolites of Cannabis sativa, and these works have shown the presence of antioxidant, antibacterial, anticoagulant, antifungal, anti-aflatoxigenic, insecticidal, anti-inflammatory, anticancer, neuroprotective and dermocosmetic activities. This paper presents the up-to-date reported investigations and opens many reflections and further research perspectives.

Archaea Carotenoids: Natural Pigments with Unexplored Innovative Potential.

For more than 40 years, marine microorganisms have raised great interest because of their major ecological function and their numerous applications for biotechnology and pharmacology. Particularly, Archaea represent a resource of great potential for the identification of new metabolites because of their adaptation to extreme environmental conditions and their original metabolic pathways, allowing the synthesis of unique biomolecules. Studies on archaeal carotenoids are still relatively scarce and only a few works have focused on their industrial scale production and their biotechnological and pharmacological properties, while the societal demand for these bioactive pigments is growing. This article aims to provide a comprehensive review of the current knowledge on carotenoid metabolism in Archaea and the potential applications of these pigments in biotechnology and medicine. After reviewing the ecology and classification of these microorganisms, as well as their unique cellular and biochemical characteristics, this paper highlights the most recent data concerning carotenoid metabolism in Archaea, the biological properties of these pigments, and biotechnological considerations for their production at industrial scale.

Bis-nor-diterpene from Cnidoscolus quercifolius (Euphorbiaceae) induces tubulin depolymerization-mediated apoptosis in BRAF-mutated melanoma cells.

A phytochemical investigation of cytotoxic extract and fractions of Cnidoscolus quercifolius Pohl led to isolation of five terpenoids, including three lupane-type triterpenes (1-3) and two bis-nor-diterpenes (4-5). Compounds 4 (phyllacanthone) and 5 (favelanone) are commonly found in this species and have unique chemical structure. Although their cytotoxic activity against cancer cells has been previously reported, the anticancer potential of these molecules remains poorly explored. In this paper, the antimelanoma potential of phyllacanthone (PHY) was described for the first time. Cell viability assay showed a promising cytotoxic activity (IC50 = 40.9 µM) against chemoresistant human melanoma cells expressing the BRAF oncogenic mutation (A2058 cell line). After 72 h of treatment, PHY inhibited cell migration and induced apoptosis and cell cycle arrest (p < 0.05). Immunofluorescence assay showed that the pro-apoptotic effect of PHY is probably associated with tubulin depolymerization, resulting in cytoskeleton disruption of melanoma cells. Molecular docking investigation confirmed this hypothesis given that satisfactory interaction between PHY and tubulin was observed, particularly at the colchicine binding site. These results suggest PHY from C. quercifolius could be potential leader for the design of new antimelanoma drugs.

Chemical Composition and Biological Screening of the Essential Oils of Micromeria macrosiphon and M. arganietorum (Lamiaceae).

The chemical composition and in vitro biological activities of the essential oil (EO) of Micromeria macrosiphon Coss. and M. arganietorum (J. Emb.) R. Morales, two Lamiaceae endemic to south Morocco, were investigated. GC/MS analysis resulted in the identification of 36 metabolites from the EO of M. macrosiphon, 45 from M. arganietorum. Borneol was the major metabolite in both oils and together with related derivatives such as camphor, accounted for 2/3 of the EO of M. macrosiphon, 1/3 of those of M. arganietorum. Pinene and terpinene derivatives were also present in high proportions. From a chemotaxonomic point of view, the composition of the examined samples may be related to those of other species endemic to Macaronesia. Both EOs showed significant toxicity towards liver HepG2 and melanoma B16 4A5 tumor cell lines at 100 µg/mL; however, they were also cytotoxic towards S17 normal cell lines, with a selectivity index <1. No antibacterial activity was noticed against 52 strains at 100 µg/mL.

Ethnobotany, phytochemistry and biological properties of Argan tree (Argania spinosa (L.) Skeels) (Sapotaceae) - A review.

ETHNOPHARMACOLOGICAL RELEVANCE: The argan [Argania spinosa (L.) Skeels] is one of the most important floristic resource in Morocco, it is the only representative of the Sapotaceae family and Argania genus found in Morocco. This tree is fully exploited by the native populations for nutrition, medication and cosmetics. The argan oil extracted from seed is the main tree product for his large use. AIM OF THE REVIEW: This review describes the traditional uses, chemical composition and biological activities of different the argan tree parts. MATERIALS AND METHODS: This review covers the literature available from 1972 to 2021. The informations were collected from electronic databases Scopus, PubMed, Web of Science, SciFinder and Google Scholar. RESULTS: Argan oil have been used for nutrition, and to treat several diseases, namely rheumatisms, hypercholesterolemia, atherosclerosis, lung infections, newborn gastrointestinal disorders, diabetes, skin and hair hydration. The other parts of Argan tree have been used to treat intestinal disorders, dermatosis, and hair caring, with additional uses such as livestock nutrition, carpentry and heating. The argan oil is primarily composed of unsaturated fatty acids mainly oleic and linoleic acids furthermore the chemical composition, of the others part, are very diversified (flavonoids, terpenoids, triacylglycerols, saponins. …). Diverse biological activities have been reported for argan oil, such as antioxidant, skin water retention, hair protection, cholesterol stabilization, antidiabetic, anticancer and antibacterial. Antimicrobial activities have been reported for argan leaves essential oils, when the fruit pulp organic extract presented very interesting antioxidant activity due to the presence of polyphenols. The argan cake is the seed waste produced during the extraction process, it is traditionally used for skin care and for livestock nutrition. Different biological activities of argan cake have been cited essentially antioxidant, haemoprotective, anti-inflammatory and antimicrobial.

A review on Moroccan Thymus species: Traditional uses, essential oils chemical composition and biological effects.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Thymus is among the most important genera in the Lamiaceae family with 215 species and is widely distributed globally, mainly in the Mediterranean region. The genus contains many medicinal plants used in traditional Moroccan medicine for a long time in treating diverse diseases. AIM OF THE REVIEW: This review describes the traditional uses, biological activities and chemical composition of essential oils (EOs) obtained from Thymus species growing in Morocco. MATERIALS AND METHODS: Information related to the traditional uses, essential oils chemical composition and biological activities on Moroccan Thymus species were obtained using the electronic databases Web of science, Scopus, SciFinder, Pubmed and Google Scholar. RESULTS: Moroccan Thymus species have been used in treatment of several diseases, namely diabetes, digestive, circulatory, genital, nervous, urinary, skin and respiratory diseases. Diverse biological activities of Moroccan Thymus species EOs have been reported, such as antibacterial, antifungal, antioxidant, anti-proliferative, anti-tumoral, insecticidal, larvicidal, nematicide, anti-inflammatory, anti-cyanobacterial and anti-acetylcholinesterase. The chemical compositions of Thymus EOs is primarily composed of monoterpenes.

Chemical Composition, Antibacterial Screening and Cytotoxic Activity of Chiliadenus antiatlanticus (Asteraceae) Essential Oil.

The chemical composition and in vitro antibacterial and cytotoxic activities of the essential oil (EO) of Chiliadenus antiatlanticus (Emb. & Maire) Gómiz, an asteraceous species endemic to the southwest of Morocco, were investigated. The EO yield was 1.07±0.28 %, twenty-seven metabolites were identified representing more than 96.4 % of the total composition. Camphor (35.7 %) and derivatives, borneol (4.9 %) and camphene (4.2 %) together with intermedeol (19.9 %), α-pinene (15.5 %) and (E)-pinocarveol (4.1 %) were the major constituents. An antibacterial activity was noticed against 24 strains (all Gram-positive) out of 71 at MICs values=100 µg/mL. The EO also showed significant toxicity towards liver HepG2 (55.8 % of cell viability) and melanoma B16 4A5 (41.6 % of cell viability) tumor cell lines at 100 µg/mL.

Synthesis of benzopyran derivatives as PPARα and/or PPARγ activators.

We describe the synthesis of 26 compounds, small polycerasoidol analogs, that are Lipinski's rule-of-five compliant. In order to confirm key structural features to activate PPARα and/or PPARγ, we have adopted structural modifications in the following parts: (i) the benzopyran core (hydrophobic nucleus) by benzopyran-4-one, dihydrobenzopyran or benzopyran-4-ol; (ii) the side chain at 2-position by shortening to C3, C4 and C5-carbons versus C-9-carbons of polycerasoidol; (iii) the carboxylic group (polar head) by oxygenated groups (hydroxyl, acetoxy, epoxide, ester, aldehyde) or non-oxygenated motifs (allyl and alkyl). Benzopyran-4-ones 6, 12, 13 and 17 as well as dihydrobenzopyrans 22, 24 and 25 were able to activate hPPARα, whereas benzopyran-4-one (7) with C5-carbons in the side chain exhibited hPPARγ agonism. According to our previous docking studies, SAR confirm that the hydrophobic nucleus (benzopyran-4-one or dihydrobenzopyran) is essential to activate PPARα and/or PPARγ, and the flexible linker (side alkyl chain) should containg at least C5-carbon atoms to activate PPARγ. By contrast, the polar head ("carboxylic group") tolerated several oxygenated groups but also non-oxygenated motifs. Taking into account these key structural features, small polycerasoidol analogs might provide potential active molecules useful in the treatment of dyslipidemia and/or type 2 diabetes.

Polycerasoidol, a Natural Prenylated Benzopyran with a Dual PPARα/PPARγ Agonist Activity and Anti-inflammatory Effect.

Dual peroxisome proliferator-activated receptor-α/γ (PPARα/γ) agonists regulate both lipid and glucose homeostasis under different metabolic conditions and can exert anti-inflammatory activity. We investigated the potential dual PPARα/γ agonism of prenylated benzopyrans polycerasoidol (1) and polycerasoidin (2) and their derivatives for novel drug development. Nine semisynthetic derivatives were prepared from the natural polycerasoidol (1) and polycerasoidin (2), which were evaluated for PPARα, -γ, -δ and retinoid X receptor-α activity in transactivation assays. Polycerasoidol (1) exhibited potent dual PPARα/γ agonism and low cytotoxicity. Structure-activity relationship studies revealed that a free phenol group at C-6 and a carboxylic acid at C-9' were key features for dual PPARα/γ agonism activity. Molecular modeling indicated the relevance of these groups for optimal ligand binding to the PPARα and PPARγ domains. In addition, polycerasoidol (1) exhibited a potent anti-inflammatory effect by inhibiting mononuclear leukocyte adhesion to the dysfunctional endothelium in a concentration-dependent manner via RXRα/PPARγ interactions. Therefore, polycerasoidol (1) can be considered a hit-to-lead molecule for the further development of novel dual PPARα/γ agonists capable of preventing cardiovascular events associated with metabolic disorders.

Production of Ramoplanin and Ramoplanin Analogs by Actinomycetes.

Ramoplanin is a glycolipodepsipeptide antibiotic obtained from fermentation of Actinoplanes sp. ATCC 33076 that exhibits activity against clinically important multi-drug-resistant, Gram-positive pathogens including vancomycin-resistant Enterococcus (VRE), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-intermediate resistant Clostridium difficile. It disrupts bacterial cell wall through a unique mechanism of action by sequestering the peptidoglycan intermediate Lipid II and therefore does not show cross-resistance with other antibiotics. However, while demonstrating excellent antimicrobial activity in systemic use in animal models of infection, ramoplanin presents low local tolerability when injected intravenously. As a consequence of this limitation, new derivatives are desirable to overcome this issue. During a natural product screening program developed to discover compounds that disrupt bacterial cell wall synthesis by inhibiting peptidoglycan transglycosylation through binding to the intermediate Lipid II, 49 actinomycete strains were identified by HR-LCMS as producers of ramoplanin-related compounds. The producing strains were isolated from environmental samples collected worldwide comprising both tropical and temperate areas. To assess the diversity of this microbial population, the 49 isolates were initially identified to the genus level on the basis of their micromorphology, and 16S sequencing confirmed the initial identification of the strains. These analyses resulted in the identification of members of genus Streptomyces, as well as representatives of the families Micromonosporaceae, Nocardiaceae, Thermomonosporaceae, and Pseudonocardiaceae, suggesting that the production of ramoplanins is relatively widespread among Actinomycetes. In addition, all of these isolates were tested against a panel of Gram-positive and Gram-negative bacteria, filamentous fungi, and yeast in order to further characterize their antimicrobial properties. This work describes the diversity of actinomycete strains that produced ramoplanin-related compounds, and the analysis of the antimicrobial activity exhibited by these isolates. Our results strongly suggest the presence of new ramoplanin-analogs among these actinomycete producers.

Dopaminergic isoquinolines with hexahydrocyclopenta[ij]-isoquinolines as D2-like selective ligands.

Dopamine receptors (DR) ligands are potential drug candidates for treating neurological disorders including schizophrenia or Parkinson's disease. Three series of isoquinolines: (E)-1-styryl-1,2,3,4-tetrahydroisoquinolines (series 1), 7-phenyl-1,2,3,7,8,8a-hexahydrocyclopenta[ij]-IQs (HCPIQs) (series 2) and (E)-1-(prop-1-en-1-yl)-1,2,3,4- tetrahydroisoquinolines (series 3), were prepared to determine their affinity for both D1 and D2-like DR. The effect of different substituents on the nitrogen atom (methyl or allyl), the dioxygenated function (methoxyl or catechol), the substituent at the ß-position of the THIQ skeleton, and the presence or absence of the cyclopentane motif, were studied. We observed that the most active compounds in the three series (2c, 2e, 3a, 3c, 3e, 5c and 5e) possessed a high affinity for D2-like DR and these remarkable features: a catechol group in the IQ-ring and the N-substitution (methyl or allyl). The series showed the following trend to D2-RD affinity: HCPIQs > 1-styryl > 1-propenyl. Therefore, the substituent at the ß-position of the THIQ and the cyclopentane ring also modulated this affinity. Among these dopaminergic isoquinolines, HCPIQs stood out for unexpected selectivity to D2-DR since the Ki D1/D2 ratio reached values of 2465, 1010 and 382 for compounds 3a, 3c and 3e, respectively. None of the most active THIQs in D2 DR displayed relevant cytotoxicity in human neutrophils and HUVEC. Finally, and in agreement with the experimental data, molecular modeling studies on DRs of the most characteristic ligands of the three series revealed stronger molecular interactions with D2 DR than with D1 DR, which further supports to the encountered enhanced selectivity to D2 DR.

Discovery of New Compounds Active against Plasmodium falciparum by High Throughput Screening of Microbial Natural Products.

Due to the low structural diversity within the set of antimalarial drugs currently available in the clinic and the increasing number of cases of resistance, there is an urgent need to find new compounds with novel modes of action to treat the disease. Microbial natural products are characterized by their large diversity provided in terms of the chemical complexity of the compounds and the novelty of structures. Microbial natural products extracts have been underexplored in the search for new antiparasitic drugs and even more so in the discovery of new antimalarials. Our objective was to find new druggable natural products with antimalarial properties from the MEDINA natural products collection, one of the largest natural product libraries harboring more than 130,000 microbial extracts. In this work, we describe the optimization process and the results of a phenotypic high throughput screen (HTS) based on measurements of Plasmodium lactate dehydrogenase. A subset of more than 20,000 extracts from the MEDINA microbial products collection has been explored, leading to the discovery of 3 new compounds with antimalarial activity. In addition, we report on the novel antiplasmodial activity of 4 previously described natural products.

Hitting the caspofungin salvage pathway of human-pathogenic fungi with the novel lasso peptide humidimycin (MDN-0010).

Fungal infections have increased dramatically in the last 2 decades, and fighting infectious diseases requires innovative approaches such as the combination of two drugs acting on different targets or even targeting a salvage pathway of one of the drugs. The fungal cell wall biosynthesis is inhibited by the clinically used antifungal drug caspofungin. This antifungal activity has been found to be potentiated by humidimycin, a new natural product identified from the screening of a collection of 20,000 microbial extracts, which has no major effect when used alone. An analysis of transcriptomes and selected Aspergillus fumigatus mutants indicated that humidimycin affects the high osmolarity glycerol response pathway. By combining humidimycin and caspofungin, a strong increase in caspofungin efficacy was achieved, demonstrating that targeting different signaling pathways provides an excellent basis to develop novel anti-infective strategies.

Efficient synthesis of hexahydroindenopyridines and their potential as melatoninergic ligands.

Hexahydroindenopyridine (HHIP) is an interesting tricyclic piperidine nucleus that is structurally related to melatonin, a serotonin-derived neurohormone. Melatonin receptor ligands have applications in several cellular, neuroendocrine and neurophysiological disorders, including depression and/or insomnia. We report herein an efficient two-step method to prepare new HHIP via enamine C-alkylation-cyclization. The influence of substituents on the benzene ring and the nitrogen atom on melatoninergic receptors has been studied. Among the 25 synthesized HHIPs, some of them containing methylenedioxy (series 2) and 8-chloro-7-methoxy substituents (series 4) on the benzene ring revealed affinity for the MT1 and/or the MT2 receptors within the nanomolar range or low micromolar. Similar activities were also encountered for those presenting urea (4g), N-aryl (2e) and N-alkyl (2f) acetamide functions. Therefore, new synthesized compounds with a HHIP nucleus have emerged as new promising leads towards the discovery of melatoninergic ligands which could provide new therapeutic agents.

High-content screening of natural products reveals novel nuclear export inhibitors.

Natural products are considered an extremely valuable source for the discovery of new drugs against diverse pathologies. As yet, we have only explored a fraction of the diversity of bioactive compounds, and opportunities for discovering new natural products leading to new drugs are huge. In the present study, U2nesRELOC, a previously established cell-based imaging assay, was employed to screen a collection of extracts of microbial origin for nuclear export inhibition activity. The fluorescent signal of untreated U2nesRELOC cells localizes predominantly to the cytoplasm. Upon treatment with the nuclear export inhibitor leptomycin B, the fluorescent-tagged reporter proteins appear as speckles in the nucleus. A proprietary collection of extracts from fungi, actinomycetes, and unicellular bacteria that covers an uncommonly broad chemical space was used to interrogate this nuclear export assay system. A two-step image-based analysis allowed us to identify 12 extracts with biological activities that are not associated with previously known active metabolites. The fractionation and structural elucidation of active compounds revealed several chemical structures with nuclear export inhibition activity. Here we show that substrates of the nuclear export receptor CRM1, such as Rev, FOXO3a and NF-κB, accumulate in the nucleus in the presence of the fungal metabolite MDN-0105 with an IC50 value of 3.4 µM. Many important processes in tumor formation and progression, as well as in many viral infections, critically depend on the nucleocytoplasmic trafficking of proteins and RNA molecules. Therefore, the disruption of nuclear export is emerging as a novel therapeutic approach with enormous clinical potential. Our work highlights the potential of applying high-throughput phenotypic imaging on natural product extracts to identify novel nuclear export inhibitors.