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The latest study published in Nature by Andrew R. Burns, Peter J. Roy and co-authors is highlighted in this paper, they investigated a series of novel nematicidal compounds, including Selectivin-A and Selectivin-E, and explored their mechanism of action. Experiments have displayed that the Selectivin compound is inactive to human cells, fish, fungi, insects and even beneficial nematodes. In the exploration of its mechanism of action, it was found that the mechanism of action of Selectivin is different with those of commercial nematocides: Selectivin needs to be activated by biotin produced by nematodes, after that they can be transformed into compounds with high nematicidal activity. This proves that the family of Selectivin compounds has the advantages of high selectivity and environmental friendliness, and their mechanism of action is completely new, proposing a completely new path for the development of new nematicides.

The latest review published in Nature Reviews Drug Discovery by Michael W. Mullowney and co-authors focuses on the use of artificial intelligence techniques, specifically machine learning, in natural product drug discovery. The authors discussed various applications of AI in this field, such as genome and metabolome mining, structural characterization of natural products, and predicting targets and biological activities of these compounds. They also highlighted the challenges associated with creating and managing large datasets for training algorithms, as well as strategies to address these obstacles. Additionally, the authors examine common pitfalls in algorithm training and offer suggestions for avoiding them.

Crops will be harmed by fungi, pests and weeds during their growth. In the past half century, scientists have conducted in-depth research on natural products extracted from microorganisms, plants or animals, and used natural products and their derivatives as the lead for pesticides discovery. Natural product pesticides have the advantages of easy degradation in the environment, selective control and safety to non-target organisms. This review summarizes the studies on natural products pesticides in recent years, including natural products of chemical modification and biosynthesis, mainly fungicides, herbicides, insecticides and acaricides. We classify natural products according to their active fragments, and discuss their effects on the control of agricultural fungi, pests and weeds. Ultimately, we found that lead discovery based on natural products has great advantages in pesticide development.

Benzoxaborole, a five-membered oxaborole ring fused with a phenyl ring, has demonstrated potent pharmacological activity. In order to explore their potential applications in agriculture, five-membered and six-membered benzoxaborole derivatives were synthesized and evaluated for their fungicidal activity against six common plant pathogenic fungi in vitro. The bioassay results showed that most of the target compounds exhibited significant fungicidal activity at concentrations below 50 μg/mL, particularly the highlighted compounds 4b and 4e, which demonstrated impressive fungicidal activity superior to those of the positive controls. Molecular docking was also performed to confirm the practical value of the active compound as a potential inhibitor of Leucyl-tRNA Synthetase (LeuRS). This study indicates that the designed benzoxaborole derivatives could serve as template molecules for the development of novel fungicides.

Abstract Here, we report an asymmetric electrochemical organonickel-catalyzed reductive cross-coupling of aryl aziridines with aryl iodides in an undivided cell, affording β-phenethylamines in good to excellent enantioselectivity with broad functional group tolerance. The combination of cyclic voltammetry analysis of the catalyst reduction potential as well as an electrode potential study provides a convenient route for reaction optimization. Overall, the high efficiency of this method is credited to the electroreduction-mediated turnover of the nickel catalyst instead of a metal reductant-mediated turnover. Mechanistic studies suggest a radical pathway is involved in the ring opening of aziridines. The statistical analysis serves to compare the different design requirements for photochemically and electrochemically mediated reactions under this type of mechanistic manifold.

Benzoazepine is a well-known pharmacophore presented in several marketed drugs. Here, the authors report the isolation and total syntheses of asperazepanones A and B from coral-derived Aspergillus candidus, two novel pyrrolinone-fused benzoazepine alkaloids with potent anti-inflammatory activities.

Quinolones can possess desirable antibacterial, antiviral and anticancer properties, rending them important synthetic targets for drug discovery purposes. Here, the gram-scale total synthesis of antiviral (+)-aniduquinolone A, possessing a 3,4-dioxygenated 5-hydroxy-4-aryl-quinolin-2(1H)-one skeleton, is reported, as well as its acid-catalyzed rearrangement to aflaquinolones A, C, and D.

Fifteen new diterpenoids, namely xishaklyanes A-O (1–15), along with three known related ones (16–18), were isolated from the soft coral Klyxum molle collected from Xisha Islands, South China Sea. The stereochemistry of the new compounds was elucidated by a combination of detailed spectroscopic analyses, chemical derivatization, quantum chemical calculations, and comparison with the reported data. The absolute configuration of compound 18 was established by the modified Mosher’s method for the first time. In bioassay, some of these compounds exhibited considerable antibacterial activities on fish pathogenic bacteria, and compound 4 showed the most effective activity with MIC of 0.225 μg/mL against Lactococcus garvieae.

Excessive inflammation causes chronic diseases and tissue damage. Although there has been drug treatment, its side effects are relatively large. Searching for effective anti-inflammatory drugs from natural products has become the focus of attention. First isolated from Trichoderma longibraciatum, trichodimerol is a natural product with TNF inhibition. In this study, lipopolysaccharide (LPS)-induced RAW264.7 macrophages were used as a model to investigate the anti-inflammatory activity of trichodimerol. The results of nitric oxide (NO) detection, enzyme-linked immunosorbent assay (ELISA), and reactive oxygen species (ROS) showed that trichodimerol could reduce the production of NO, ROS, and the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Western blotting results showed that trichodimerol could inhibit the production of inflammatory mediators such as cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) and the protein expression of nuclear transcription factor-kappaB (NF-κB), p-IKK, p-IκB, Toll-like receptor 4 (TLR4), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), cysteinyl aspartate specific proteinase (Caspase)-1, and ASC, which indicated that trichodimerol may inhibit inflammation through the NF-κB and NLRP3 pathways. At the same time, molecular docking showed that trichodimerol can directly combine with the TLR4-MD2 complex. Hence, trichodimerol inhibits inflammation by obstructing the interaction between LPS and the TLR4-MD2 heterodimer and suppressing the downstream NF-κB and NLRP3 pathways.

Background: Excessive inflammation results in severe tissue damage as well as serious acute or chronic disorders, and extensive research has focused on finding new anti-inflammatory hit compounds with safety and efficacy profiles from natural products. As promising therapeutic entities for the treatment of inflammation-related diseases, fusaproliferin and its analogs have attracted great interest. However, the underlying anti-inflammatory mechanism is still poorly understood and deserves to be further investigated.Methods: For the estimation of the anti-inflammatory activity of fusaproliferin (1) and its analogs (2-4)in vitro and in vivo, lipopolysaccharide (LPS)-induced RAW264.7 macrophages and zebrafish embryos were employed. Then, transcriptome analysis was applied to guide subsequent western blot analysis of critical proteins in related signaling pathways. Surface plasmon resonance assays (SPR) combined with molecular docking analyses were finally applied to evaluate the affinity interactions between 1-4 and TLR4 and provide a possible interpretation of the downregulation of related signaling pathways.Results: 1-4 significantly attenuated the production of inflammatory messengers, including nitric oxide (NO), reactive oxygen species (ROS), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), as well as nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in LPS-induced RAW264.7 macrophages. Transcriptome analyses based on RNA-seq indicated the ability of compound 1 to reverse LPS stimulation and the nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPKs) signaling pathways contribute to the anti-inflammatory process. Experimental verification at the protein level revealed that 1 can inhibit the activation of inhibitor of NF-κB kinase (IKK), degradation of inhibitor of NF-κB (IκB), and phosphorylation of NF-κB and reduce nuclear translocation of NF-κB. 1 also decreased the phosphorylation of MAPKs, including p38, extracellular regulated protein kinases (ERK), and c-Jun N-terminal kinase (JNK). SPR assays and molecular docking results indicated that 1-4 exhibited affinity for the TLR4 protein with KD values of 23.5–29.3 μM.Conclusion: Fusaproliferin and its analogs can be hit compounds for the treatment of inflammation-associated diseases.

Based on the structures of natural products streptochlorin and pimprinine derived from marine or soil microorganisms, a series of streptochlorin derivatives containing the nitrile group were designed and synthesized through acylation and oxidative annulation. Evaluation for antifungal activity showed that compound 3a could be regarded as the most promising candidate—it demonstrated over 85% growth inhibition against Botrytis cinerea, Gibberella zeae, and Colletotrichum lagenarium, as well as a broad antifungal spectrum in primary screening at the concentration of 50 μg/mL. The SAR study revealed that non-substituent or alkyl substituent at the 2-position of oxazole ring were favorable for antifungal activity, while aryl and monosubstituted aryl were detrimental to activity. Molecular docking models indicated that 3a formed hydrogen bonds and hydrophobic interactions with Leucyl-tRNA Synthetase, offering a perspective for the possible mechanism of action for antifungal activity of the target compounds.

Pimprinine and streptochlorin are indole alkaloids derived from marine or soil microorganisms. In our previous study, they were promising lead compounds due to their potent bioactivity in preventing many phytopathogens, but further structural modifications are required to improve their antifungal activity. In this study, pimprinine and streptochlorin were used as parent structures with the combination strategy of their structural features. Three series of target compounds were designed and synthesized. Subsequent evaluation for antifungal activity against six common phytopathogenic fungi showed that some of thee compounds possessed excellent effects, and this is highlighted by compounds 4a and 5a, displaying 99.9% growth inhibition against Gibberella zeae and Alternaria Leaf Spot under 50 μg/mL, respectively. EC50 values indicated that compounds 4a, 5a, 8c, and 8d were even more active than Azoxystrobin and Boscalid. SAR analysis revealed the relationship between 5-(3′-indolyl)oxazole scaffold and antifungal activity, which provides useful insight into the development of new target molecules. Molecular docking models indicate that compound 4a binds with leucyl-tRNA synthetase in a similar mode as AN2690, offering a perspective on the mode of action for the study of its antifungal activity. These results suggest that compounds 4a and 5a could be regarded as novel and promising antifungal agents against phytopathogens due to their valuable potency.

Chlrosulfuron, a classical sulfonylurea herbicide that exhibits good safety for wheat but causes a certain degree of damage to subsequent corn in a wheat–corn rotation mode, has been suspended field application in China since 2014. Our previous study found that diethylamino-substituted chlorsulfuron derivatives accelerated the degradation rate in soil. In order to obtain sulfonylurea herbicides with good crop safety for both wheat and corn, while maintaining high herbicidal activities, a series of pyrimidine- and triazine-based diethylamino-substituted chlorsulfuron derivatives (W102–W111) were systematically evaluated. The structures of the synthesized compounds were confirmed with 1H NMR, 13C NMR, and HRMS. The preliminary biological assay results indicate that the 4,6-disubstituted pyrimidine and triazine derivatives could maintain high herbicidal activity. It was found that the synthesized compounds could accelerate degradation rates, both in acidic and alkaline soil. Especially, in alkaline soil, the degradation rate of the target compounds accelerated more than 22-fold compared to chlorsulfuron. Moreover, most chlorsulfuron analogs exhibited good crop safety for both wheat and corn at high dosages. This study provided a reference for the further design of new sulfonylurea herbicides with high herbicidal activity, fast degradation rates, and high crop safety.

Sulfonylurea herbicides are widely used as acetolactate synthase (ALS) inhibitors due to their super-efficient activity. However, some sulfonylurea herbicides show toxicity under crop rotation due to their long degradation time, for example, chlorsulfuron. Our research goal is to obtain chlorsulfuron-derived herbicides with controllable degradation time, good crop safety and high herbicidal activities. Based on our previously reported results in acidic soil, we studied the degradation behaviors of 5-dialkylamino-substituted chlorsulfuron derivatives (NL101–NL108) in alkaline soil (pH 8.39). The experimental data indicate that addition of the 5-dialkylamino groups on the benzene ring of chlorsulfuron greatly accelerated degradation in alkaline soil. These chlorsulfuron derivatives degrade 10.8 to 51.8 times faster than chlorsulfuron and exhibit excellent crop safety on wheat and corn (through pre-emergence treatment). With a comprehensive consideration of structures, bioassay activities, soil degradation and crop safety, it could be concluded that 5-dialkylamino-substituted chlorsulfuron derivatives are potential green sulfonylurea herbicides for pre-emergence treatment on both wheat and corn. The study also provides valuable information for the discovery of new sulfonylurea herbicides for crop rotation.

Four new sesquiterpene hydroquinones, xishaeleganins A–D (6–9), along with eleven known related ones (12 and 14–23) were isolated from the Xisha marine sponge Dactylospongia elegans (family Thorectida). Their structures were determined by extensive spectroscopic analysis, ECD calculations, and by comparison with the spectral data reported in the literature. Compounds 7, 15, 20, and 21 showed significant antibacterial activity against Staphylococcus aureus, with minimum inhibitory concentration values of 1.5, 2.9, 5.6, and 5.6 µg/mL, which are comparable with those obtained for the positive control vancomycin (MIC: 1.0 µg/mL).

Brefeldin A (1), a potent cytotoxic natural macrolactone, was produced by the marine fungus Penicillium sp. (HS-N-29) from the medicinal mangrove Acanthus ilicifolius. Series of its ester derivatives 2–16 were designed and semi-synthesized, and their structures were characterized by spectroscopic methods. Their cytotoxic activities were evaluated against human chronic myelogenous leukemia K562 cell line in vitro, and the preliminary structure–activity relationships revealed that the hydroxy group played an important role. Moreover, the monoester derivatives exhibited stronger cytotoxic activity than the diester derivatives. Among them, brefeldin A 7-O-2-chloro-4,5-difluorobenzoate (7) exhibited the strongest inhibitory effect on the proliferation of K562 cells with an IC50 value of 0.84 µM. Further evaluations indicated that 7 induced cell cycle arrest, stimulated cell apoptosis, inhibited phosphorylation of BCR-ABL, and thereby inactivated its downstream AKT signaling pathway. The expression of downstream signaling molecules in the AKT pathway, including mTOR and p70S6K, was also attenuated after 7-treatment in a dose-dependent manner. Furthermore, molecular modeling of 7 docked into 1 binding site of an ARF1–GDP-GEF complex represented well-tolerance. Taken together, 7 had the potential to be served as an effective antileukemia agent or lead compound for further exploration.

Summary: The CF3O functional group is a unique fluorinated group that has received a great deal of attention in medicinal chemistry and agrochemistry. However, trifluoromethoxylation of substrates remains a challenging task. Herein we describe the dehydroxytrifluoromethoxylation of alcohols promoted by a R3P/ICH2CH2I (R3P = Ph3P or Ph2PCH=CH2) system in DMF. P-I halogen bonding drives the reaction of R3P with ICH2CH2I in DMF to generate iodophosphonium salt (R3P+I I−) and a Vilsmeier-Haack-type intermediate, both of which could effectively activate alcohols, thus enabling a fast (15 min) trifluoromethoxylation reaction. A wide substrate scope and a high level of functional group tolerance were observed. : Chemistry; Organic Chemistry; Organic Synthesis Subject Areas: Chemistry, Organic Chemistry, Organic Synthesis

Fifteen polyketides, including four new compounds, isoversiol F (1), decumbenone D (2), palitantin B (7), and 1,3-di-O-methyl-norsolorinic acid (8), along with 11 known compounds (3–6 and 9–15), were isolated from the deep-sea-derived fungus Aspergillus versicolor SH0105. Their structures and absolute configurations were determined by comprehensive spectroscopic data, including 1D and 2D NMR, HRESIMS, and ECD calculations, and it is the first time to determine the absolute configuration of known decumbenone A (6). All of these compounds were evaluated for their antimicrobial activities against four human pathogenic microbes and five fouling bacterial strains. The results indicated that 3,7-dihydroxy-1,9-dimethyldibenzofuran (14) displayed obvious inhibitory activity against Staphylococcus aureus (ATCC 27154) with the MIC value of 13.7 μM. In addition, the antioxidant assays of the isolated compounds revealed that aspermutarubrol/violaceol-I (15) exhibited significant 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity with the IC50 value of 34.1 μM, and displayed strong reduction of Fe3+ with the ferric reducing antioxidant power (FRAP) value of 9.0 mM under the concentration of 3.1 μg/mL, which were more potent than ascorbic acid.

Water spinach (I. aquatica) is one of the common green leafy vegetables used in Asia. In a continuing chemical investigation on the cytotoxic resin glycosides from water spinach, eight new resin glycosides, Aquaterins XII–XIX (1–8), were isolated, among which 1, 2 and 4 exhibited potent cytotoxic activities. To further characterise the anticancer potential of the resin glycosides from water spinach, Aquaterin II obtained previously was investigated on HepG2 cells. The results showed that Aquaterin II induced G0/G1 arrest regulated by related proteins CDK4/6, cyclin D/E and p21, and caused mitochondria-mediated apoptosis featured by MMP decrease, ROS accumulation, caspase cascade activation and Bax/Bcl-2 alteration. Additionally, the suppression on PI3K/Akt signalling pathway was observed, suggesting that it participated in the Aquaterin II-induced cell growth inhibition. Our results are the first to demonstrate the antiproliferative mechanism of resin glycosides. This investigation also advanced the potential application of water spinach as a functional food.

Two new terpene glycosides (1−2) along with two known analogs (3−4) were obtained from the root of Sanguisorba officinalis, which is a common traditional Chinese medicine (TCM). Their structures were elucidated by nuclear magnetic resonance (NMR), electrospray ionization high resolution mass spectrometry (HRESIMS), and a hydrolysis reaction, as well as comparison of these data with the literature data. Compounds 1−4 exhibited anti-inflammatory properties in vitro by attenuating the production of inflammatory mediators, such as nitric oxide (NO) as well as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). An anti-inflammatory assay based on the zebrafish experimental platform indicated that compound 1 had good anti-inflammatory activity in vivo by not only regulating the distribution, but also by reducing the amount of the macrophages of the zebrafish exposed to copper sulfate.

Three new thiodiketopiperazines (1–3), along with two known analogues (4 and 5), were isolated from the fermentation broth of Penicillium crustosum. Their structures were elucidated through extensive spectroscopic analysis and the absolute configurations of new compounds were determined by Mosher ester analysis and calculated ECD spectra. Compound 4 and 5 have the activity to promote the gastrointestinal motility of zebrafish via acting on the cholinergic nervous system.

Five new polyketides, including two pairs of enantiomers and a racemate, were isolated from the fermentation broth of Aspergillus fumigatus, an endophytic fungus isolated from Cordyceps sinensis. Their structures were identified using one-dimensional (1D) and two-dimensional (2D) NMR experiments, and the absolute configurations of the enantiomers were confirmed using electronic circular dichroism (ECD) calculations. Compounds 1a and 2a exhibited inhibitory activity against the MV4-11 cell line in vitro, with IC50 values of 23.95 µM and 32.70 µM, respectively.

Nine new angucycline glycosides designated urdamycins N1–N9 (1–9), together with two known congener urdamycins A (10) and B (11), were obtained from a mangrove-derived Streptomyces diastaticus subsp. SCSIO GJ056. The structures of new compounds were elucidated on the basis of extensive spectroscopic data analysis. The absolute configurations of 6–9 were assigned by electronic circular dichroism calculation method. Urdamycins N7 (7) and N8 (8) represent the first naturally occurring (5R, 6R)-angucycline glycosides, which are diastereomers of urdamycins N6 (6) and N9 (9), respectively.

A new prenyleudesmane type diterpene, sinupol (8), and a new capnosane type diterpenoid, sinulacetate (9), were isolated from the Xisha soft coral Sinularia polydactyla along with five known related diterpenes (4–7 and 10). Their structures, including absolute configurations, were determined by extensive spectroscopic analysis, the comparison of their NMR data with those of related compounds, and time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculations. Both new compounds (8 and 9) exhibited promising inhibitory activity against protein tyrosine phosphatase 1B (PTP1B), a potential drug target for the treatment of type II diabetes and obesity.

A new centrosymmetric cyclohexapeptide, aspersymmetide A (1), together with a known peptide, asperphenamate (2), was isolated from the fungus Aspergillus versicolor isolated from a gorgonian coral Carijoa sp., collected from the South China Sea. The chemical structure of 1 was elucidated by analyzing its NMR spectroscopy and MS spectrometry data, and the absolute configurations of the amino acids of 1 were determined by Marfey’s method and UPLC-MS analysis of the hydrolysate. Aspersymmetide A (1) represents the first example of marine-derived centrosymmetric cyclohexapeptide. Moreover, 1 exhibited weak cytotoxicity against NCI-H292 and A431 cell lines at the concentration of 10 μM.