Fourteen eremophilane sesquiterpenoids (1-14), including nine new congeners, septoreremophilanes A-I (1-9), together with three known sesquiterpenes (15-17), two known tetralone derivatives (18, 19), and two known cholesterol analogues (20, 21), were isolated from the endophytic fungus Septoria rudbeckiae. Compounds 1-6 and 7a belong to the family of the highly oxygenated eremophilane sesquiterpenoids with a 6/6/5 tricyclic system and bearing a hemiacetal moiety. The inhibitions of all metabolites against eight bacteria were estimated in vitro, and nine new metabolites (1-9) were tested for antineuroinflammatory activity. Notably, the effects of 4 against Pseudomonas syringae pv. actinidae and 20 against Bacillus cereus displayed potent inhibitory, with the MIC values of 6.25 and 6.25 μM, respectively. Further, scanning electron microscopy analyses indicated that 4 and 20 were to change the outer configuration of bacterial cells, respectively, and the investigations demonstrated that 4 and 20 may act as potential structure templates for the development of the agrochemical bactericides. Additionally, compound 6 displayed potent inhibition of NO generation in lipopolysaccharide-induced BV-2 microglial cells (IC50 = 12.0 ± 0.32 μM), and the conceivable anti-inflammatory mechanisms implicated were also investigated by molecular docking. Thus, the bioactive metabolites of the strain S. rudbeckiae may serve as a novel resource to be developed.

Eremophilane Sesquiterpenoids with Antibacterial and Anti-inflammatory Activities from the Endophytic Fungus Septoria rudbeckiae.

Indole is a popular and functional scaffold existing widely in the fields of medicine, pesticides, spices, food and feed additives, dyes, and many others. Among indoles, 2-arylindole represents a particular and interesting subset but has attracted less attention for drug discovery. In this study, we report a general, practical one-pot assembly of a variety of 2-arylindole derivatives. To develop novel fungicide scaffolds, their fungicide activity was also evaluated. The bioassay results showed that many of the synthesized 2-arylindoles exhibited considerable fungicidal activities especially toward Rhizoctonia cerealis, and several demonstrated an inhibition rate of more than 90%. Notably, 4-fluoro-2-phenyl-1H-indole 6e was obtained with a broad spectrum of fungicidal activities, which showed excellent growth inhibition activities against R. cerealis, Rhizoctonia solani, Botrytis cinerea, Magnaporthe oryza, and Sclerotinia sclerotiorum with EC50 values of 2.31, 4.98, 6.78, 10.57, and 17.80 μg/mL, respectively. Preliminary fungicidal mode of action of 6e showed a significant inhibition effect on mycelial growth and spore germination. These results indicated that 2-arylindoles as privileged scaffolds exhibited potential fungicidal activities that deserve further study.

2-Arylindoles: Concise Syntheses and a Privileged Scaffold for Fungicide Discovery.

Two new polyketides named rufoolivacin E and viocristin B, a new natural product named 1-hydroxy-3,6,8-trimethoxyanthraquinone, and 13 known compounds were isolated from edible mushroom Cortinarius purpurascens in this work. Their structures were assigned on the basis of high-resolution electrospray ionization mass spectrometry, 1D and 2D nuclear magnetic resonance, and electronic circular dichroism data. Notably, the enzyme activity test on glutamate dehydrogenase indicated that 1, 3, 4, 5, 6, 10, 11, and 15 displayed an excellent inhibition effect. Further kinetic studies showed that the most potent compounds, 4 and 10, possess great potential as competitive inhibitors of glutamate dehydrogenase. Molecular docking and computational chemistry were applied to illustrate the binding mechanism in detail. 2,2-Diphenyl-1-picrylhydrazyl and reactive oxygen species assay results showed that compounds 1, 2, 3, and 8 exhibited significant antioxidant activities with IC50 values of 7.0 ± 0.3, 8.6 ± 0.1, 7.5 ± 0.1, and 2.8 ± 0.2 μg mL-1, respectively. Thus, Cortinarius caerulescens represents a novel resource of these polyketides to be utilized in food selection and drug discovery.

Bioactive Monomer and Polymer Polyketides from Edible Mushroom Cortinarius caerulescens as Glutamate Dehydrogenase Inhibitors and Antioxidants.

In this study, a series of novel mesoionic pyrido[1,2-a]pyrimidinone compounds containing a natural skeleton indole were designed and synthesized, and the insecticidal activities of the target compounds were tested. The results showed that the target compounds had good to excellent insecticidal activities against white-backed planthoppers (Sogatella furcifera) and bean aphids (Aphis craccivora). Among them, compound 7 showed outstanding insecticidal activities against both S. furcifera and A. craccivora, with LC50 values of 0.86 and 0.85 μg/mL, respectively. The insecticidal activity against bean aphids (A. craccivora) was superior to that of triflumezopyrim (LC50 = 3.67 μg/mL). Proteomics and quantitative real-time polymerase chain reaction (qRT-PCR) results revealed that compound 7 may interact with α1 and α7 nAChR subunits of S. furcifera. The results of enzyme activities indicated that compound 7 was an inhibitor of AChE in S. furcifera. This study provides new ideas for the discovery of new mesoionic pyrido[1,2-a]pyrimidinone insecticides.

Design, Synthesis, and Insecticidal Activity of Novel Pyrido[1, 2-a]pyrimidinone Mesoionic Compounds Containing an Indole Moiety as Potential Acetylcholine Receptor Insecticides.

Anti-aflatoxigenic nano-emulsions based on Monarda didyma and Neopallasia pectinata essential oils as novel green agent for food preservation

Sixteen metabolites, including seven C7-alkylated salicylaldehyde derivatives (1-7) and nine prenylated indole alkaloids (8-16), three of which are new, namely, asperglaucins A and B (1 and 2) and neoechinulin F (8), were separated from the endolichenic fungus Aspergillus chevalieri SQ-8. Asperglaucin A (1) represents an unusual phthalide-like derivative with a benzo[c]thiophen-1(3H)-one scaffold. All compounds were assessed in vitro for antibacterial, antineuroinflammatory, and antioxidant activities. Notably, asperglaucins A and B exhibited potent antibacterial activities against two plant pathogens Pseudomonas syringae pv actinidae (Psa) and Bacillus cereus, with an MIC value of 6.25 μM; further SEM analyses illustrated that the possible bacteriostatic mechanisms for compounds 1 and 2 were to alter the external structure of B. cereus and Psa, and to cause the rupture or deformation of the cell membranes, respectively, and the results suggest that compounds 1 and 2 may serve as potential promising candidates for lead compounds of agrochemical bactericides. Furthermore, compounds 6 and 10 significantly inhibited nitric oxide production with an IC50 value of ca. 12 μM, and the possible anti-inflammatory mechanisms involved were also studied by molecular docking. Finally, the tested phenolics 3-5 showed significant antioxidative effects. Thus, strain SQ-8 represents a novel resource of these bioactive metabolites to be utilized.

Yi-Meng Wang

Papers

Alkylated Salicylaldehydes and Prenylated Indole Alkaloids from the Endolichenic Fungus Aspergillus chevalieri and Their Bioactivities.