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Sarcodon mushrooms are esteemed as a rare and highly valuable resource for both culinary and medicinal purposes. Ancient medical classics have documented their beneficial effects on conditions such as indigestion, loss of appetite, and neurological disorders. Modern phytochemical research into their secondary metabolites has led to the discovery of numerous bioactive compounds with significant biological activities. Despite notable achievements in the study of the chemical composition and bioactivity of Sarcodon mushrooms, a comprehensive understanding of these findings has been lacking. This review provides an exhaustive summary of the advancements in the phytochemistry of Sarcodon mushrooms, as well as the biological and pharmacological activities of the isolated compounds and crude extracts derived from Sarcodon over the past nine decades. A total of 100 secondary metabolites isolated from these mushrooms have been classified into five major categories based on their chemical structures, which exhibit bioactivities such as anti-tumour, neurotrophic, and neuroprotective, antioxidant, anti-inflammatory, antimicrobial, and hypoglycaemic properties. The aim of this study is to establish a scientific foundation for future research in drug discovery, biotechnological development, and the exploration of functional foods involving Sarcodon mushrooms.

The family Diatrypaceae is a less well-known group within the order Xylariales (Ascomycota). Initially, the focus on its metabolites was related to the pathogenicity of one of its members, Eutypa lata. To date, a total of 254 natural products have been identified from Diatrypaceae strains. These compounds include terpenoids, sterols, polyketones, phenols, and acetylene aromatic compounds, which have shown anticancer, cytotoxic, anti-inflammatory, antimicrobial, and antiviral activities. The complex and diverse structural types, along with the diverse bioactivities, highlight the potential of Diatrypaceae as a valuable source of bioactive natural products. In this review, a deep analysis of the biosynthesis of pimarane diterpenes and scoparasin-type cytochalasins is provided, coupled with a compilation of the biosynthetic pathways of aromatic acetylene compounds in filamentous fungi. This comprehensive review not only enhances our understanding of the natural product chemistry, biological activities, and biosynthesis of secondary metabolites from the Diatrypaceae family but also promotes the exploitation and development of important bioactive compounds and potential strains.

Abstract Radical S‐adenosyl‐L‐methionine (SAM) enzymes couple the reductive cleavage of SAM to radical‐mediated transformations that have proven to be quite broad in scope. DesII is one such enzyme from the biosynthetic pathway of TDP‐desosamine where it catalyzes a radical‐mediated deamination. Previous studies have suggested that this reaction proceeds via direct elimination of ammonia from an α‐hydroxyalkyl radical or its conjugate base (i.e., a ketyl radical) rather than 1,2‐migration of the amino group to form a carbinolamine radical intermediate. However, without a crystal structure, the active site features responsible for this chemistry have remained largely unknown. The crystallographic studies described herein help to fill this gap by providing a structural description of the DesII active site. Computational analyses based on the solved crystal structure are consistent with direct elimination and indicate that an active site glutamate residue likely serves as a general base to promote deprotonation of the α‐hydroxyalkyl radical intermediate and elimination of the ammonia group.

Abstract Glycosylation is a prevalent post-modification found in natural products and has a significant impact on the structural diversity and activity variation of natural products. Glucosylation is the most common type of glycosylation, whereas xylosylation is relatively rare. Despite their unique chemical structures and beneficial activities, xylosylated natural products from microorganisms have received little attention. This review provides, for the first time, a comprehensive summary of 126 microbial-derived xylosylated natural products, including xylosyl-cyathane diterpenes, xylosylated triterpenes, xylosyl aromatic compounds, and others. Among these compounds, xylosyl-cyathane diterpenes represent the highest number of derivatives, followed by xylosylated triterpenes. Xylosyl compounds from bacterial sources have less defined structural profiles compared to those from fungi. The characterization of xylosyltransferase EriJ from Basidiomycota extended the structural diversity of xylosyl cyathane diterpenes. This work provides a valuable reference for the research and use of xylosyltransferase for drug discovery and synthetic chemistry. Further work is needed to explore the potential applications of microbial derived xylosyl compounds and to develop novel xylosyl transferases. With the deepening of genomic sequencing of medicinal fungi, more biosynthesis of bioactive xylosyl compounds is expected to be elucidated in the future. Graphical Abstract

Abstract The search for lead compounds with anti-neuroinflammatory activity from structurally ‘optimized’ natural products is a crucial and promising strategy in the quest to discover safe and efficacious agents for treating neurodegenerative diseases. A phytochemical investigation on the aerial portions of Hypericum elatoides led to the isolation of five nitrogenous polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperelanitriles A–D (1–4) and hyperelamine A (5). Their structures were determined by spectroscopic analysis, ECD and NMR calculations, and X-ray crystallography. To the best of our knowledge, compounds 1–4 represent the first examples of acylphloroglucinols featuring an α-aminonitrile moiety, while 5 is a rare enamine-containing PPAP. Further, the synthesis of these naturally occurring PPAP-based nitriles or amines was accomplished. Compound 5 exhibited inhibitory activity against LPS-activated NO production in BV-2 cells, potentially through the suppression of TLR-4/NF-κB signaling. Here we show the isolation, structural elucidation, synthesis, and bioactive evaluation of compounds 1–5.

Abstract Mushrooms have been utilized by humans for thousands of years due to their medicinal and nutritional properties. They are a crucial natural source of bioactive secondary metabolites, and recent advancements have led to the isolation of several alkynyl-containing compounds with potential medicinal uses. Despite their relatively low abundance, naturally occurring alkynyl compounds have attracted considerable attention due to their high reactivity. Bioactivity studies have shown that alkynyl compounds exhibit significant biological and pharmacological activities, including antitumor, antibacterial, antifungal, insecticidal, phototoxic, HIV-inhibitory, and immunosuppressive properties. This review systematically compiles 213 alkynyl-containing bioactive compounds isolated from mushrooms since 1947 and summarizes their diverse biological activities, focusing mainly on cytotoxicity and anticancer effects. This review serves as a detailed and comprehensive reference for the chemical structures and bioactivity of alkynyl-containing secondary metabolites from mushrooms. Moreover, it provides theoretical support for the development of chemical constituents containing alkynyl compounds in mushrooms based on academic research and theory. Graphical Abstract

Abstract Indole diterpenoids (IDTs) are an essential class of structurally diverse fungal secondary metabolites, that generally appear to be restricted to a limited number of fungi, such as Penicillium, Aspergillus, Claviceps, and Epichloe species, etc. These compounds share a typical core structure consisting of a cyclic diterpene skeleton of geranylgeranyl diphosphate (GGPP) and an indole ring moiety derived from indole-3-glycerol phosphate (IGP). 3-geranylgeranylindole (3-GGI) is the common precursor of all IDTs. On this basis, it is modified by cyclization, oxidation, and prenylation to generate a large class of compounds with complex structures. These compounds exhibit antibacterial, anti-insect, and ion channel inhibitory activities. We summarized 204 compounds of IDTs discovered from various fungi over the past 50 years, these compounds were reclassified, and their biological activities were summarized. This review will help to understand the structural diversity of IDTs and provide help for their physiological activities. Graphical Abstract

Six ionone glycosides (1–3 and 5–7), including three new ones, named capitsesqsides A−C (1–3), together with an eudesmane sesquiterpenoid glycoside (4) and three known triterpenoid saponins (8–10) were isolated from Rhododendron capitatum. The structures of these compounds were determined by extensive spectroscopic techniques (MS, UV, 1D-NMR, and 2D-NMR) and comparison with data reported in the literature. The absolute configurations were determined by comparison of the experimental and theoretically calculated ECD curves and LC-MS analyses after acid hydrolysis and derivatization. The anti-inflammatory activities of these compounds were evaluated in the LPS-induced RAW264.7 cells. Molecular docking demonstrated that 2 has a favorable affinity for NLRP3 and iNOS.

Abstract Background Cyclic dipeptides are an important class of natural products owing to their structural diversity and biological activities. In fungi, the cyclo-ring system is formed through the condensation of two α-amino acids via non-ribosomal peptide synthetase (NRPS). However, there are few investigations on the functional identification of this enzyme. Additionally, information on how to increase the production of cyclic dipeptide molecules is relatively scarce. Results We isolated the Eurotium cristatum NWAFU-1 fungus from Jing-Wei Fu brick tea, whose fermentation metabolites contain echinulin-related cyclic dipeptide molecules. We cloned the cirC gene, encoding an NRPS, from E. Cristatum NWAFU-1 and transferred it into the heterologous host Aspergillus oryzae. This transformant produced a novel metabolite possessing an l-tryptophan-l-alanine cyclic dipeptide backbone (Cyclo-TA). Based on the results of heterologous expression and microsomal catalysis, CriC is the first NRPS characterized in fungi that catalyzes the formation of a cyclic dipeptide from l-tryptophan and l-alanine. After substrate feeding, the final yield reached 34 mg/L. In this study, we have characterized a novel NRPS and developed a new method for cyclic dipeptide production. Conclusions In this study we successfully expressed the E. Cristatum NWAFU-1 criC gene in A. oryzae to efficiently produce cyclic dipeptide compounds. Our findings indicate that the A. oryzae heterologous expression system constitutes an efficient method for the biosynthesis of fungal Cyclic dipeptides.

Abstract Background Inonotus obliquus is an important edible and medicinal mushroom that was shown to have many pharmacological activities in preclinical trials, including anti-inflammatory, antitumor, immunomodulatory, and antioxidant effects. However, the biosynthesis of these pharmacological components has rarely been reported. The lack of genomic information has hindered further molecular characterization of this mushroom. Results In this study, we report the genome of I. obliquus using a combined high-throughput Illumina NovaSeq with Oxford Nanopore PromethION sequencing platform. The de novo assembled 38.18 Mb I. obliquus genome was determined to harbor 12,525 predicted protein-coding genes, with 81.83% of them having detectable sequence similarities to others available in public databases. Phylogenetic analysis revealed the close evolutionary relationship of I. obliquus with Fomitiporia mediterranea and Sanghuangporus baumii in the Hymenochaetales clade. According to the distribution of reproduction-related genes, we predict that this mushroom possesses a tetrapolar heterothallic reproductive system. The I. obliquus genome was found to encode a repertoire of enzymes involved in carbohydrate metabolism, along with 135 cytochrome P450 proteins. The genome annotation revealed genes encoding key enzymes responsible for secondary metabolite biosynthesis, such as polysaccharides, polyketides, and terpenoids. Among them, we found four polyketide synthases and 20 sesquiterpenoid synthases belonging to four more types of cyclization mechanism, as well as 13 putative biosynthesis gene clusters involved in terpenoid synthesis in I. obliquus. Conclusions To the best of our knowledge, this is the first reported genome of I. obliquus; we discussed its genome characteristics and functional annotations in detail and predicted secondary metabolic biosynthesis-related genes, which provides genomic information for future studies on its associated molecular mechanism.

ABSTRACT The prevalence of superbugs, represented by methicillin-resistant Staphylococcus aureus (MRSA), has become a serious clinical and public safety concern with rising incidence in hospitals. Polyketides with diverse chemical structures harbor many antimicrobial activities, including those of rifampin and rapamycin against MRSA. Streptomyces sp. QHH-9511 was isolated from a niche habitat in the Qinghai-Tibet Plateau and used to produce antibacterial metabolites. Herein, an integrated approach combining genome mining and metabolic analysis were employed to decipher the chemical origin of the antibacterial components with pigmented properties in strain QHH-9511, a novel Streptomyces species from a lichen symbiont on the Qinghai-Tibet Plateau. Genomic phylogeny assembled at the chromosome level revealed its unique evolutionary state. Further genome mining uncovered 36 candidate gene clusters, most of which were uncharacterized. Meanwhile, based on liquid chromatography coupled to diode array detection mass spectrometry, a series of granaticins, BSMs, chromones, phaeochromycins, and related molecules were discovered by using the Global Natural Product Social molecular networking platform. Subsequently, several pigment compounds were isolated and identified by high-resolution mass spectrometry and/or nuclear magnetic resonance, among which the structure-activity relationships of seven aromatic polyketides showed that the fused lactone ring of the C-2 carboxyl group could increase antibacterial activity. Genetic experiments indicated that all seven aromatic polyketides are a series of metabolic shunts produced by a single type II polyketide synthase (PKS) cluster. Comparative genomic analysis of granaticin producers showed that the granaticin gene cluster is widely distributed. This study provides an efficient method to combine genome mining and metabolic profiling techniques to uncover bioactive metabolites derived from specific habitats, while deepening our understanding of aromatic polyketide biosynthesis. IMPORTANCE Undescribed microorganisms from special habitats are being screened for anti-superbug drug molecules. In a project to screen actinomycetes for anti-MRSA activity, we isolated a Streptomyces strain from Qinghai Lake lichens. The phylogeny based on the genome assembled at the chromosome level revealed this strain's unique evolutionary state. The chemical origins of the antibacterial components with pigment properties in strain QHH-9511 were determined using an integrated approach combining genome mining and metabolic analysis. Further genome mining uncovered 36 secondary metabolite gene clusters, the majority of which were previously unknown. A series of aromatic compounds were discovered using molecular network analysis, separation, and extraction. Genetic experiments revealed that all seven aromatic polyketides are a series of metabolic shunts produced by a single cluster of type II PKSs. This study describes a method for identifying novel Streptomyces from specific habitats by combining genome mining with metabolic profiling techniques.

ABSTRACT Laetiporus sulphureus mushroom is a complementary and alternative medicine that has anticancer, antioxidation, and analgesic effects and immunomodulatory activity; it is used as a treatment for cough and rheumatism and is a functional food that can improve physical fitness. Even though L. sulphureus has garnered considerable biotechnological and pharmacological interest due to its excellent cellulose-degrading ability and diverse biological activities, its biosynthetic potential regarding polysaccharides and secondary metabolites has not been thoroughly examined. In this study, we sequenced and assembled the whole genome of a wild L. sulphureus isolate, NWAFU-1, from the Qinling Mountains in China. Comparative genomes analysis revealed genomic differences between subspecies, and phylogenomic analysis revealed evolutionary divergence as well as genome expansion and contraction of individual Polyporaceae family species. Bioinformatics investigation identified candidate genes associated with mating type, polysaccharide synthesis, carbohydrate-active enzymes, and secondary-metabolite biosynthesis, which included multiple terpenoids, nonribosomal peptides, and polyketides. The locations of biosynthetic core genes were mapped and displayed on chromosomes and contigs. Totals of 143 proteins from 126 coding genes were identified and divided into 14 cytochrome P450 families. Furthermore, the biosynthetic network of tetracyclic triterpenoid active components was postulated by genome mining of related genes combined with the molecular network of metabolites. The genome analysis of L. sulphureus in this study improves the understanding of the biosynthesis of active compounds, which will lay a theoretical foundation for subsequent research on active-compound biosynthesis and promote the application of Laetiporus in the field of drug research and functional-food creation. IMPORTANCE L. sulphureus is a parasitic basidiomycete fungus that causes brown rot. The fruiting bodies of L. sulphureus are used as ancient medicines in China and Europe to cure cancer, analgesia, cough, and rheumatism and are considered a functional food that regulates the body and improves health. L. sulphureus was inferred to be a tetrapolar system based on a high-quality genome, which will aid molecular breeding and artificial farming. Screening polysaccharide synthesis candidate genes and comparing carbohydrate-associated genes in brown-rot basidiomycetes help understand their growth. Identifying core genes for secondary-metabolite biosynthesis, gene cluster family analysis, and comparative cluster analysis will guide heterologous-biosynthesis investigations of these genes and help elucidate the biosynthetic pathways for L. sulphureus bioactive natural components. The biosynthesis network of tetracyclic triterpenes was mapped using metabolite profiling and genome scanning. This work explores the biosynthetic capacity of L. sulphureus-derived natural products and lays the foundation for biosynthetic studies of them.

Alzheimer's disease (AD) is a neurodegenerative disease in which oxidative stress and neuroinflammation were demonstrated to be associated with neuronal loss and cognitive deficits. However, there are still no specific treatments that can prevent the progression of AD. In this study, a screening of anti-inflammatory hits from 4207 natural compounds of two different molecular libraries indicated 1,6-O,O-diacetylbritannilactone (OABL), a 1,10-seco-eudesmane sesquiterpene lactone isolated from the herb Inula britannica L., exhibited strong anti-inflammatory activity in vitro as well as favorable BBB penetration property. OABL reduced LPS-induced neuroinflammation in BV-2 microglial cells as assessed by effects on the levels of inflammatory mediators including NO, PGE2, TNF-α, iNOS, and COX-2, as well as the translocation of NF-κB. Besides, OABL also exhibited pronounced neuroprotective effects against oxytosis and ferroptosis in the rat pheochromocytoma PC12 cell line. For in vivo research, OABL (20 mg/kg B.W., i.p.) for 21 d attenuated the impairments in cognitive function observed in 6-month-old 5xFAD mice, as assessed with the Morris water maze test. OABL restored neuronal damage and postsynaptic density protein 95 (PSD95) expression in the hippocampus. OABL also significantly reduced the accumulation of amyloid plaques, the Aβ expression, the phosphorylation of Tau protein, and the expression of BACE1 in AD mice brain. In addition, OABL attenuated the overactivation of microglia and astrocytes by suppressing the expressions of inflammatory cytokines, and increased glutathione (GSH) and reduced malondialdehyde (MDA) and super oxide dismutase (SOD) levels in the 5xFAD mice brain. In conclusion, these results highlight the beneficial effects of the natural product OABL as a novel treatment with potential application for drug discovery in AD due to its pharmacological profile.

A series of novel steroidal C-20 oxime ester derivatives were prepared from 16-DPA, and their structures were characterized by IR, 1D-NMR and ESI-MS methods. The compounds were tested against NB4, PC-3 and HeLa cancer cells in vitro, five of which showed potent cytotoxicity. Preliminary results indicated that structure modification of C-20 oxime ester may have potential cytotoxicity. Keywords: 16-DPA, Steroidal, Oxime ester, Cytotoxicity

In the original publication, there were publisher errors in the names of authors Zhen-xin Wang, Xi-long Feng and Jin-ming Gao and affiliation (1) of the first, second, fourth and fifth authors (name of the Key Laboratory and city) [...]

Inonotus hispidus mushroom is a traditional medicinal fungus with anti-cancer, antioxidation, and immunomodulatory activities, and it is used in folk medicine as a treatment for indigestion, cancer, diabetes, and gastric illnesses. Although I. hispidus is recognized as a rare edible medicinal macrofungi, its genomic sequence and biosynthesis potential of secondary metabolites have not been investigated. In this study, using Illumina NovaSeq combined with the PacBio platform, we sequenced and de novo assembled the whole genome of NPCB_001, a wild I. hispidus isolate from the Aksu area of Xinjiang Province, China. Comparative genomic and phylogenomic analyses reveal interspecific differences and evolutionary traits in the genus Inonotus. Bioinformatics analysis identified candidate genes associated with mating type, polysaccharide synthesis, carbohydrate-active enzymes, and secondary metabolite biosynthesis. Additionally, molecular networks of metabolites exhibit differences in chemical composition and content between fruiting bodies and mycelium, as well as association clusters of related compounds. The deciphering of the genome of I. hispidus will deepen the understanding of the biosynthesis of bioactive components, open the path for future biosynthesis research, and promote the application of Inonotus in the fields of drug research and functional food manufacturing.

Sesterterpenes are 25-carbon terpenoids formed by the cyclization of dimethyl allyl diphosphate (DMAPP) and isopentenyl diphosphate (IPP) as structural units by sesterterpenes synthases. Some (not all) sesterterpenoids are modified by cytochrome P450s (CYP450s), resulting in more intricate structures. These compounds have significant physiological activities and pharmacological effects in anti-inflammatory, antibacterial, antitumour, and hypolipidemic communities. Despite being a rare class of terpenoids, sesterterpenoids derived from fungi show a wide range of structural variations. The discovered fungal sesterterpenoid synthases are composed of C-terminal prenyltransferase (PT) and N-terminal terpene synthase (TS) domains, which were given the name PTTSs. PTTSs have the capacities to catalyze chain lengthening and cyclization concurrently. This review summarizes all 52 fungal PTTSs synthases and their biosynthetic pathways involving 100 sesterterpenoids since the discovery of the first PTTSs synthase from fungi in 2013.

Sesquiterpenes are common small-molecule natural products with a wide range of promising applications and are biosynthesized by sesquiterpene synthase (STS). Basidiomycetes are valuable and important biological resources. To date, hundreds of related sesquiterpenoids have been discovered in basidiomycetes, and the biosynthetic pathways of some of these compounds have been elucidated. This review summarizes 122 STSs and 2 fusion enzymes STSs identified from 26 species of basidiomycetes over the past 20 years. The biological functions of enzymes and compound structures are described, and related research is discussed.

Inonotus hispidus mushroom is a popular edible and medicinal mushroom with a long history of use. It is well known as a medicinal fungus with various health benefits for its significant anticancer and immunomodulatory activities. Over the last 60 years, secondary metabolites derived from I. hispidus and their biological activities have been discovered and investigated. Structurally, these compounds are mainly polyphenols and triterpenoids, which have anticancer, anti-inflammatory, antioxidant, antimicrobial, and enzyme inhibitor activities. Here, the secondary metabolites derived from I. hispidus and their activities were systematically and comprehensively classified and summarized, and the biosynthetic pathway of stylylpyrones was deduced and analyzed further. This review contributes to our understanding of I. hispidus and will help with research into natural product chemistry, pharmacology, and the biosynthesis of I. hispidus metabolites. According to this review, I. hispidus could be a promising source of bioactive compounds for health promotion and the development of functional foods.

In this article, 23 compounds (6 and 7a–7v) were prepared and evaluated for their in vitro α-glucosidase inhibitory activity. The compounds 7d, 7f, 7i, 7n, 7o, 7r, 7s, 7u, and 7v displayed the α-glucosidase inhibition activity with IC50 values ranging from 1.68 to 7.88 µM. Among all tested compounds, 7u was found to be the most efficient, being 32-fold more active than the standard drug acarbose, which significantly attenuated postprandial blood glucose in mice. In addition, the compound 7u also induced the fluorescence quenching and conformational changes of enzyme, by forming α-glucosidase–7u complex in a mixed inhibition type. The thermodynamic constants recognised the interaction between 7u and α-glucosidase and was an enthalpy-driven spontaneous exothermic reaction. The synchronous fluorescence and CD spectra also indicate that the compound 7u changed the enzyme conformation. The findings identify the binding interactions between new ligands and α-glucosidase and reveal the compound 7u as a potent α-glucosidase inhibitor.

Abstract Ten new polyoxygenated cyathane diterpenoids, named neocyathins A–J (1–10), together with four known diterpenes (11–14), were isolated from the liquid culture of the medicinal basidiomycete fungus Cyathus africanus. The structures and configurations of these new compounds were elucidated through comprehensive spectroscopic analyses including 1D NMR, 2D NMR (HSQC, HMBC, NOESY) and HRESIMS, and electronic circular dichroism (ECD) data. Neuroinflammation is implicated in the pathogenesis of various neurodegenerative diseases, such as Alzheimers’ disease (AD). All isolated compounds were evaluated for the potential anti-neuroinflammatory activities in BV2 microglia cells. Several compounds showed differential effects on the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated and Aβ1–42-treated mouse microglia cell line BV-2. Molecular docking revealed that bioactive compounds (e.g., 11) could interact with iNOS protein other than COX-2 protein. Collectively, our results suggested that this class of cyathane diterpenoids might serve as important lead compounds for drug discovery against neuroinflammation in AD.

Mosquito-transmitted Plasmodium parasites cause millions of people worldwide to suffer malaria every year. Drug-resistant Plasmodium parasites and insecticide-resistant mosquitoes make malaria hard to control. Thus, the next generation of antimalarial drugs that inhibit malaria infection and transmission are needed. We screened our Global Fungal Extract Library (GFEL) and obtained a candidate that completely inhibited Plasmodium falciparum transmission to Anopheles gambiae. The candidate fungal strain was determined as Aspergillus aculeatus. The bioactive compound was purified and identified as asperaculane B. The concentration of 50% inhibition on P. falciparum transmission (IC50) is 7.89 µM. Notably, asperaculane B also inhibited the development of asexual P. falciparum with IC50 of 3 µM, and it is nontoxic to human cells. Therefore, asperaculane B is a new dual-functional antimalarial lead that has the potential to treat malaria and block malaria transmission.

We describe the efficient synthesis of a series of new simplified hamigeran B and 1-hydroxy-9-epi-hamigeran B norditerpenoid analogs (23 new members in all), structurally related to cyathane diterpenoid scaffold, and their anti-neuroinflammatory and neurite outgrowth-stimulating (neurotrophic) activity. Compounds 9a, 9h, 9o, and 9q exhibited moderate nerve growth factor (NGF)-mediated neurite-outgrowth promoting effects in PC-12 cells at the concentration of 20 μm. Compounds 9b, 9c, 9o, 9q, and 9t showed significant nitric oxide (NO) production inhibition in lipopolysaccharide (LPS)-activated BV-2 microglial cells, of which 9c and 9q were the most potent inhibitors, with IC50 values of 5.85 and 6.31 μm, respectively. Two derivatives 9q and 9o as bifunctional agents displayed good activities as NO production inhibitors and neurite outgrowth-inducers. Cytotoxicity experiments, H2O2-induced oxidative injury assay, and ELISA reaction speculated that compounds may inhibit the TNF-α pathway to achieve anti-inflammatory effects on nerve cells. Moreover, molecular docking studies provided a better understanding of the key structural features affecting the anti-neuroinflammatory activity and displayed significant binding interactions of some derivatives (like 9c, 9q) with the active site of iNOS protein. The structure-activity relationships (SARs) were also discussed. These results demonstrated that this structural class compounds offered an opportunity for the development of a new class of NO inhibitors and NGF-like promotors.

Six sesquiterpenoids 1–6, including two new ones, an ent-daucane-type sesquiterpenoid, asperaculane A (1), and a nordaucane one, asperaculane B (2), and four known nordaucane derivatives, aculenes A–D 3–6, together with the known secalonic acid D (7), were isolated from a fermentation culture of the fungus Aspergillus aculeatus. Their structures and absolute configurations were established by analyses of their spectroscopic data, including 1D and 2D-NMR spectra, HR-ESIMS, electronic circular dichroism (ECD) data, and quantum chemical calculations. These metabolites were evaluated for in vitro cytotoxic activity against two cell lines, human cancer cell lines (HeLa) and one normal hamster cell line (CHO).

In order to establish an advanced structural-activity relationship (SAR) and to explore the feasibility of kakuol analogues with better anti-fungi activity, a series of 2-hydroxy-4,5-methylenedioxyaryl ketones were conveniently synthesized by the Friedel-Crafts acyl reaction, etherification reaction, reduction reaction and oximation reaction. Their structures characterized by 1H and 13C NMR and HRMS methods. Their in vitro antifungal activities were assayed. Most of the derivatives showed a remarkable in vitro activity, and some of them appeared significantly more effective than a commercial fungicide hymexazol as positive control. In particular compounds 2h and 2i, were found active with a IC50 value of 3.1 mg/ml and 2.9 mg/ml against Glomerella cingulate, which suggested that 2-hydroxy-4,5-methylenedioxyaryl ketones might be a promising candidates in the development of new antifungal compounds. Compounds 2e, 5 and 6 also exhibited high antifungal activities on a wide range of organisms, which might be considered as leading compounds in the development of new antifungal compounds.DOI: http://doi.dx.org/10.5564/mjc.v15i0.331 Mongolian Journal of Chemistry 15 (41), 2014, p94-100

A new etherified 1-O-acetylbritannilactone (ABL) analogue 2 was semi-synthesized by a mild etherification reaction. The structure of the newly synthesized analogue was identified by 1H-NMR, 13C-NMR and HR-ESI-MS analysis. 2 exhibited similar cytotoxicity against HCT116, SGC-7901 and HeLa human cancer cell lines with ABL.

Two tartary buckwheat samples (Xingku No.2 and Diqing) grown at three locations were analyzed for free and bound phenolic content and antioxidant properties. Moreover, the relative contributions of variety and growing environment to phenolic content and antioxidant properties were determined, as well as correlations of these properties to growing conditions. The total phenolic contents varied from 5,150 to 9,660 μmol of gallic acid equivalents per 100 gram of dry weight (DW) of tartary buckwheat and the free phenolics accounted for 94% to 99%. Rutin content was in the range from 518.54 to 1,447.87 mg per 100 gram of DW of tartary buckwheat. p-Hydroxybenzoic, ferulic and protocatechuic acids were the prominent phenolic acids and other phenolics, including p-coumaric, gallic, caffeic, vanillic and syringic acids were also detected. Tartary buckwheat exhibited higher DPPH· and ABTS·+ scavenging activities and was more effective at preventing the bleaching of β-carotene in comparison with reference antioxidant and plant phenolics constituents. Additionally, growing conditions and the interaction between variety and environment may have more contribution than variety to individual phenolics and antioxidant properties of tartary buckwheat. Environmental parameters such as higher altitudes may also have an increasing effect on rutin and phenolic acids. This study suggests that tartary buckwheat has potential health benefits because of its high phenolic content and antioxidant properties. These components could also be enhanced by optimizing the growing conditions of a selected variety.

Sulfonated (SO3H-bearing) activated carbon (AC-SO3H) was synthesized by an aryl diazonium salt reduction process. The obtained material had a SO3H density of 0.64 mmol·g-1 and a specific surface area of 602 m2·g-1. The catalytic properties of AC-SO3H were compared with that of two commercial solid acid catalysts, Nafion NR50 and Amberlyst-15. In a 10-h esterification reaction of acetic acid with ethanol, the acid conversion with AC-SO3H (78%) was lower than that of Amberlyst-15 (86%), which could be attributed to the fact that the SO3H density of the sulfonated carbon was lower than that of Amberlyst-15 (4.60 mmol·g-1). However, AC-SO3H exhibited comparable and even much higher catalytic activities than the commercial catalysts in the esterification of aliphatic acids with longer carbon chains such as hexanoic acid and decanoic acid, which may be due to the large specific surface area and mesoporous structures of the activated carbon. The disadvantage of AC-SO3H is the leaching of SO3H group during the reactions.

Based on benzoxazole and benzothiazole scaffold as an important pharmacophore, two series of 2-(aryloxymethyl) benzoxazole and benzothiazole derivatives were synthesized and their antifungal effects against eight phytopathogenic fungi were evaluated. Compounds 5a, 5b, 5h, and 5i exhibited significant antifungal activities against most of the pathogens tested. Especially 5a, 5b, 5h, 5i, 5j, and 6h inhibited the growth of F. solani with IC50 of 4.34–17.61 μg/mL, which were stronger than that of the positive control, hymexazol (IC50 of 38.92 μg/mL). 5h was the most potent inhibitor (IC50 of 4.34 μg/mL) against F. Solani, which was about nine times more potent than hymexazol. Most of the test compounds displayed significant antifungal effects against B. cinerea (IC50 of 19.92–77.41 μg/mL), among them, 5a was the best one (IC50 of 19.92 μg/mL). The structure-activity relationships (SARs) were compared and analyzed. The result indicates that the electron-drawing ability and position of the substituents have a significant impact on biological activities. Furthermore, docking studies were carried out on the lipid transfer protein sec14p from S. cerevisiae, and preliminarily verified the antifungal activities. Taken together, these results provide 2-(phenoxymethyl)benzo[d]oxazole as an encouraging framework that could lead to the development of potent novel antifungal agents.

Three new grayanane diterpenoids, pierisoids C‒E (1–3), as well as 10 known ones (4–13), were evaluated from the flowers of Pieris formosa, which is used as an insecticide in rural areas of China. Their structures were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analyses. Significant antifeedant activity of 1, 3 and 10 against the beet armyworm (Spodoptera exigua) was found, indicating that these diterpenoids might also be involved in the plant defense against insect herbivores.

The title compound, C10H13ClN2O, was obtained as a by-product in the reaction of 2-chloromethyl-1H-benzimidazole, dimethyl sulfate and toluene to synthesise 2-chloromethyl-1-methylbenzimidazole. The dihedral angle between the benzene ring and the acetamide group is 89.72 (6)° while that between the aromatic ring and the chloracetyl group is 84.40 (4)°. In the crystal, adjacent molecules are linked by pairs of N—H...O hydrogen bonds into inversion dimers.

Four new unsaturated aliphatic acid amides, named zanthoamides A–D (1–4), and eight known ones—tetrahydrobungeanool (5), ZP-amide A (6), ZP-amide B (7), ZP-amide C (8), ZP-amide D (9), ZP-amide E (10), bugeanumamide A (11), and (2E,7E,9E)-N-(2-hydroxy-2-methylpropyl)-6,11-dioxo-2,7,9-dodecatrienamide (12)—were isolated from the pericarps of Zanthoxylum bungeanum. The structures of these compounds were elucidated by extensive use of spectroscopic methods, including HRESIMS, 1D and 2D NMR analyses and comparison with previously reported data. Compound 4 contained a rare C6 fatty acid unit with an acetal group. Results revealed that compounds 1, 5, 6, and 12 showed inhibitory effects on nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages, with IC50values of 48.7 ± 0.32, 27.1 ± 1.15, 49.8 ± 0.38, and 39.4 ± 0.63 µM, respectively, while the other compounds were inactive (IC50 > 60 μM). They could contribute to the anti-inflammatory effects of Z. bungeanum by suppression of NO production.

Two picrotoxane sesquiterpene lactone glycosides, nepalactones A (1) and B (2), and one new coumarin, nepalarin (3), were isolated from the root barks of the poisonous plant Coriaria nepalensis. Their structures were elucidated via HRESIMS and 1D and 2D NMR spectroscopic analyses, and further verified via transformation methods. In addition, compounds 1–3 and five semisynthetic congeners (1a–e) were assayed for the activity to induce neurite outgrowth in rat pheochromocytoma (PC12) cells. As a result, nepalactone A derivative 1c and nepalarin (3) significantly enhanced nerve growth factor (NGF)-mediated neurite outgrowth in PC12 cells.

The title compound, C16H14Cl2O4S, was obtained by the reaction of eugenol (4-allyl-2-methoxyphenol) and 3,4-dichlorobenzenesulfonyl chloride. The dihedral angle between the benzene rings in the molecule is 40.53 (4)°. No significantly short intermolecular contacts are observed in the crystal structure.

The title compound, C13H11Cl2N3O2, was obtained by the reaction of eugenol and cyanuric chloride. The dihedral angle between the benzene and triazine rings is 87.56 (4)°. Two C atoms of the allyl group are disordered over two sites in a 0.72 (2):0.28 (2) ratio.

In the title compound, C15H12F2O2, the dihedral angle between the aromatic rings is 70.43 (4)°. The crystal packing exhibits no significantly short intermolecular contacts.

The title compound, C15H12F2O3, has been obtained by the reaction of 2,4-dihydroxylacetonephenone, potassium carbonate and 3,5-difluorobenzyl bromide. The hydroxy group is involved in an intramolecular O—H...O hydrogen bond in each of the two independent molecules in the asymmetric unit. The dihedral angle between the aromatic rings is 0.5 (2)° in one molecule and 1.9 (2)° in the other. In the crystal, weak C—H...O interactions link the molecules into tetrameric units aligned perpendicular to b.

The title compound, C11H13ClO3, has been obtained in the reaction of 2, 4-dihydroxylacetonephenone, potassium carbonate and 1-bromo-3-chloro-hexane. The hydroxy group is involved in an intramolecular O—H...O hydrogen bond. The crystal packing exhibits no significantly short intermolecular contacts

In the title compound, C13H9BrO2, the benzene and furan rings form a dihedral angle of 44.35 (14)°. The crystal packing exhibits no significantly short intermolecular contacts.