Trichodermates A–F,New Cytotoxic Trichothecenes from the Plant Pathogenic Fungus Trichoderma sp.

Trichodermates A – F ( 1 – 6 , resp.), six new trichothecene polyunsaturated octadioic acid esters, and (?)‐harzianum B ( 7 ) were isolated from the fermentation extract of Trichoderma sp., a plant pathogenic fungus isolated from stem rot of an unidentified tree in Thailand. The structures of 1 – 7 were elucidated by NMR experiments. The absolute configuration at C(12) in 3 was assigned by in situ dimolybdenum circular dichroism method, whereas that in 7 was deduced after hydrolysis of 7 to 8 via modified Mosher's method. Compounds 1 and 2 showed modest cytotoxic activities against the K562 (human myelogenous leukemia) cell line with IC₅₀ values of 12.12 and 13.08 μM , respectively.     

Neocornuside A–D,Four Novel Iridoid Glycosides from Fruits of Cornus officinalis and Their Antidiabetic Activity

Four previously undescribed iridoid glycosides neocornuside A–D (1–4), along with six known ones (5–10), were isolated from Cornus officinalis fruit. Their structures were elucidated by extensive spectroscopic (NMR, UV, IR, and MS) analysis and comparison with data reported in the literature. All isolates were assessed for their antidiabetic activity on the relative glucose consumption in insulin-induced insulin-resistant HepG2 cells. The results showed that compounds 1, 3, and 7 exhibited significant antidiabetic activities with EC₅₀ values of 0.582, 1.275, and 0.742 μM, respectively. Moreover, compounds 1, 3, and 7 could improve the ability of 2-NBDG uptake of insulin-induced HepG2 cells.     

New Lactone and Xanthone Derivatives Produced by a Mangrove Endophytic Fungus Phoma sp. SK3RW1M from the South China Sea

A new lactone, 1,8‐dihydroxy‐10‐methoxy‐3‐methyldibenzo[b,e]oxepine‐6,11‐dione ( 1 ), and two new xanthones, 1‐hydroxy‐8‐(hydroxymethyl)‐6‐methoxy‐3‐methyl‐9H‐xanthen‐9‐one ( 2 ) and 1‐hydroxy‐8‐(hydroxymethyl)‐3‐methoxy‐6‐methyl‐9H‐xanthen‐9‐one ( 3 ), were isolated from a mangrove endophytic fungus Phoma sp. SK3RW1M collected from the South China Sea. This is the first report on xanthone derivatives isolated as secondary metabolites from Phoma species. Their structures were elucidated by spectroscopic methods, mainly 1D‐ and 2D‐NMR techniques, and the structure of compound 2 was confirmed by X‐ray crystallography. Cytotoxicity assays showed that compounds 1 – 3 were inactive against KB and KBv200 cells.     

Chromone Derivatives with α-Glucosidase Inhibitory Activity from the Marine Fungus Penicillium thomii Maire

The fungal strain YPGA3 was isolated from the sediments of the Yap Trench and identified as Penicillium thomii. Eight new chromone derivatives, named penithochromones M−T (1–8), along with two known analogues, 9 and 10, were isolated from the strain. The structures were established by detailed analyses of the spectroscopic data. The absolute configuration of the only chiral center in compound 1 was tentatively determined by comparing the experimental and the calculated specific rotations. Compounds 7 and 8 represent the first examples of chromone derivatives featuring a 5,7-dioxygenated chromone moiety with a 9-carbon side chain. Bioassay study revealed that compounds 6–10 exhibited remarkable inhibition against α-glucosidase with IC₅₀ values ranging from 268 to 1017 μM, which are more active than the positive control acarbose (1.3 mmol).     

Shuangancistrotectorines A–E,Dimeric Naphthylisoquinoline Alkaloids with Three Chiral Biaryl Axes from the Chinese Plant Ancistrocladus tectorius

Five novel dimeric naphthylisoquinoline alkaloids, shuangancistrotectorines A ( 3 a ), B ( 3 b ), C ( 4 ), D ( 5 a ), and E ( 5 b ), have been isolated from the twigs of the Chinese plant Ancistrocladus tectorius. Their absolute stereostructures were determined by spectroscopic and chiroptical methods in combination with quantum chemical CD calculations. In contrast to all other known dimeric naphthylisoquinoline alkaloids, in which the central binaphthalene axis is 6′,6′′‐coupled and thus not rotationally hindered, the dimers described here are linked via the sterically more hindered 3′,3′′‐ or 1′,1′′‐positions of the naphthalene units. They are thus the first such dimers—and even the very first natural products at all—that have three consecutive stereogenic axes. Hence, including the stereogenic centers, they have up to seven stereogenic units in total. Some of the compounds, in particular shuangancistrotectorines A, B, and D ( 3 a , 3 b , and 5 a ) exhibit very good, and specific, antiplasmodial activities.     

Lentzeacins A-E,New Bacterial-Derived 2,5- and 2,6-Disubstituted Pyrazines from a BGC-Rich Soil Bacterium Lentzea sp. GA3-008

Pyrazines (1,4-diazirines) are an important group of natural products that have tremendous monetary value in the food and fragrance industries and can exhibit a wide range of biological effects including antineoplastic, antidiabetic and antibiotic activities. As part of a project investigating the secondary metabolites present in understudied and chemically rich Actinomycetes, we isolated a series of six pyrazines from a soil-derived Lentzea sp. GA3-008, four of which are new. Here we describe the structures of lentzeacins A-E (1, 3, 5 and 6) along with two known analogues (2 and 4) and the porphyrin zincphyrin. The structures were determined by NMR spectroscopy and HR-ESI-MS. The suite of compounds present in Lentzea sp. includes 2,5-disubstituted pyrazines (compounds 2, 4, and 6) together with the new 2,6-disubstituted isomers (compounds 1, 3 and 5), a chemical class that is uncommon. We used long-read Nanopore sequencing to assemble a draft genome sequence of Lentzea sp. which revealed the presence of 40 biosynthetic gene clusters. Analysis of classical di-modular and single module non-ribosomal peptide synthase genes, and cyclic dipeptide synthases narrows down the possibilities for the biosynthesis of the pyrazines present in this strain.     

New Helvolic Acid Derivatives with Antibacterial Activities from Sarocladium oryzae DX-THL3, an Endophytic Fungus from Dongxiang Wild Rice (Oryza rufipogon Griff.)

Three new helvolic acid derivatives (named sarocladilactone A (1), sarocladilactone B (2) and sarocladic acid A (3a)), together with five known compounds (6,16-diacetoxy-25-hy- droxy-3,7-dioxy-29-nordammara-1,17(20)-dien-21-oic acid (3b), helvolic acid (4), helvolinic acid (5), 6-desacetoxy-helvolic acid (6) and 1,2-dihydrohelvolic acid (7)), were isolated from the endophytic fungus DX-THL3, obtained from the leaf of Dongxiang wild rice (Oryza rufipogon Griff.). The structures of the new compounds were elucidated via HR-MS, extensive 1D and 2D NMR analysis and comparison with reported data. Compounds 1, 2, 4, 5, 6 and 7 exhibited potent antibacterial activities. In particular, sarocladilactone B (2), helvolinic acid (5) and 6-desacetoxy-helvolic acid (6) exhibited strongly Staphylococcus aureus inhibitory activity with minimum inhibitory concentration (MIC) values of 4, 1 and 4 μg/mL, respectively. The structure–activity relationship (SAR) of these compounds was primarily summarized.     

Anthraquinone Derivatives and an Orsellinic Acid Ester from the Marine Alga‐Derived Endophytic Fungus Eurotium cristatum EN‐220

Cultivation of the fungal strain Eurotium cristatum EN‐220, an endophyte obtained from the marine alga Sargassum thunbergii, resulted in the isolation of one new anthraquinone glycoside, 3‐O‐(α‐D ‐ribofuranosyl)questinol ( 1 ) and one new orsellinic acid ester, cristatumside A ( 2 ), together with three known aromatic glycosides, 3‐O‐(α‐D ‐ribofuranosyl)questin ( 3 ), isotorachrysone 6‐O‐α‐D ‐ribofuranoside ( 4 ), and asperflavin ribofuranoside ( 5 ), as well as three anthraquinone derivatives, asperflavin ( 6 ), eurorubrin ( 7 ), and (+)‐variecolorquinone A ( 8 ). The structures of these compounds were determined by extensive analysis of their spectroscopic data, as well as by their comparison with those in the literature. Each of the isolated compounds was evaluated for its antimicrobial activity and brine shrimp lethality.     

A New Inorganic‐Organic Hybrid with Zinc Phosphate Layers Pillared by the 4, 4'‐Bipyridine Units

A new inorganic‐organic hybrid zinc phosphate with the formula Zn₂(4, 4'‐bipy)(HPO₄)₂ (4, 4'‐bipy = 4, 4'‐bipyridine) has been synthesized under hydrothermal conditions and characterized by single‐crystal X‐ray diffraction, FTIR, ICP analysis, elemental analysis, SEM, powder X‐ray diffraction, thermogravimetric analysis and its fluorescent spectrum. The compound crystallizes in the monoclinic system, space group P2₁/c (No.14), a = 10.4479(7), b = 8.1694(5), c = 8.9643(5) Å, β = 97.907(2), V = 757.86(8) ų, Z = 2. The structure consists of ZnO₃N and HPO₄ tetrahedra by corner‐sharing to generate neutral 4.8²‐net sheets, which are pillared through 4, 4'‐bipy ligands to form a 3‐D hybrid framework.     

(±)-Cryptamides A–D,Four Pairs of Novel Dopamine Enantiomer Trimers from the Periostracum Cicadae

Four pairs of novel dopamine enantiomer trimers, (±)-cryptamides A–D (1–4), and 10 pairs of previously described dopamine enantiomer dimers (5–14) were isolated from the Periostracum cicadae, the cast-off shell of the insect Cryptotympana pustulata. Aside from being pairs of enantiomers, the eight trimers were also elucidated to be regioisomers, most likely resulting from their mechanism of formation, [4 + 2] cycloaddition. The discovery of dopamine trimers is rarely reported when it comes to natural products derived from insects.     

Sarcoglycosides A – C,New O‐Glycosylglycerol Derivatives from the South China Sea Soft Coral Sarcophyton infundibuliforme

Chemical examination of the soft coral Sarcophyton infundibuliforme collected from the South China Sea resulted in the isolation of the three new O‐glycosylglycerol derivatives sarcoglycosides A–C ( 1 – 3 ), together with two known compounds, chimyl alcohol ( 4 ) and hexadecanol ( 5 ). Their structures were elucidated by combined spectral and chemical methods. All the compounds showed moderate toxicity to brine shrimps Artemia salina.     

Parvaxanthines D–F and Asponguanosines C and D,Racemic Natural Hybrids from the Insect Cyclopelta parva

Five new compounds including three pairs of enantiomeric xanthine analogues, parvaxanthines D–F (1–3), two new guanosine derivatives, asponguanosines C and D (6 and 7), along with two known adenine derivatives were isolated from the insect Cyclopelta parva. Racemic 1–3 were further separated by chiral HPLC. Their absolute configurations were assigned by spectroscopic and computational methods. It is interesting that all of these isolates are natural product hybrids. Antiviral, immunosuppressive, antitumor and anti-inflammatory properties of all the isolates were evaluated.     

Design,Synthesis, Crystal Structure,In Vitro and In Silico Evaluation of New N′-Benzylidene-4-tert-butylbenzohydrazide Derivatives as Potent Urease Inhibitors

Background: Hydrazides play a vital role in making biologically active compounds in various fields of chemistry. These determine antioxidant, antidepressant, antimalarial, anti-inflammatory, antiglycating, and antimicrobial activity. In the present study, twenty-three new N′ benzylidene-4-(tert-butyl)benzohydrazide derivatives (4–26) were synthesized by the condensation of aromatic aldehydes and commercially available 4-(tert-butyl)benzoic acid. All the target compounds were successfully synthesized from good to excellent yield; all synthesized derivatives were characterized via spectroscopic techniques such as HREI-MS and ¹H-NMR. Synthesized compounds were evaluated for in vitro urease inhibition. All synthesized derivatives demonstrated good inhibitory activities in the range of IC₅₀ = 13.33 ± 0.58–251.74 ± 6.82 µM as compared with standard thiourea having IC₅₀ = 21.14 ± 0.425 µM. Two compounds, 6 and 25, were found to be more active than standard. SAR revealed that electron donating groups in phenyl ring have more influence on enzyme inhibition. However, to gain insight into the participation of different substituents in synthesized derivatives on the binding interactions with urease enzyme, in silico (computer simulation) molecular modeling analysis was carried out.     

Design,Synthesis, Antifungal Activities and SARs of (R)‐2‐Aryl‐4,5‐dihydrothiazole‐4‐carboxylic Acid Derivatives

Based on the structure of natural product 2‐aryl‐4,5‐dihydrothiazole‐4‐carboxylic acid, a series of novel (R)‐2‐aryl‐4,5‐dihydrothiazole‐4‐carboxylic acid derivatives were designed and synthesized. Their structures were characterized by ¹H NMR, ¹³C NMR and HRMS. The single crystal structure of compound 9b was determined by X‐ray diffraction analysis. The antifungal activities were evaluated for the first time. The bioassay results indicated that most compounds exhibited moderate to good antifungal activities. The antifungal activities of compound 13a (against Cercospora arachidicola Hori), 13d (against Alternaria solani), and 16e (against Cercospora arachidicola Hori) were 61.9%, 67.3% and 61.9%, respectively, which are higher than those of the commercial fungicides chlorothalonil and carbendazim. Moreover, compound 13d exhibited excellent antifungal activities against 7 kinds of the fungi tested (66.7%, 77.3%, 63.0%, 87.9%, 70.0%, 70.0% and 80.0% at 50 µg?mL). Therefore, 13d can be used as a new lead structure for the development of antifungal agents.     

Hydrothermal Synthesis, Crystal Structure and Luminescence Properties of a New 2D Cadmium Complex Based on the 4,4'-Bis(benzimidazol-1-ylmethy1)biphenyl and Glutaric Acid Ligands

A new polymeric complex {Cd2(bbmb)2(gt)2·(H2O)2}n (bbmb = 4,4'-bis(benzimidazol-1-ylmethy1)biphenyl, H2gt = glutaric acid) has been obtained by hydrothermal method and structurally characterized by elemental analysis, IR, XRD, TGA and single-crystal X-ray diffraction. The complex belongs to the triclinic system, space group P1 with a = 10.2417(15), b = 13.752(2), c = 22.201(3), α = 73.899(2), β = 88.416(2), γ = 78.305(2)°, V = 2940.4(7)3 , Z = 2, C66H56Cd2N8O8 , Mr = 1313.99, Dc = 1.484 g/cm3 , F(000) = 1336 and μ= 0.787 mm-1 , and features a 2D network. In the solid state at room temperature, the cadmium(Ⅱ) complex exhibits strong fluorescence absorption at 435 nm (λmax).     

New silicate-germanate Cs2Pb2[(Si0.6Ge0.4)2O7] from the series A2Pb2[B2O7], A = K,Cs, B = Si,Ge with the umbrella-like [PbO3]4- group

New silicate-germanate Cs₂Pb₂[(Si_0.6Ge_0.4)₂O₇] was synthesized in multi-components hydrothermal solution with 20 w.% concentration of Cs₂CO₃ mineralizer, pH = 10. Novel mixed compound belongs to the structure type A₂Pb₂[B₂O₇] previously indicated for powders with A = K, B=Si or Ge. Singe crystal structure determination of Cs₂Pb₂[(Si_0.6Ge_0.4)₂O₇] revealed the need for the correction of the space group of the earlier suggested structural model from P-3 to P-3m1, as well as for the splitting of the Pb-atom position. Umbrella-like groups [PbO₃]^4- are located between [(Si,Ge)O₄]^4- tetrahedra in mica-like honeycomb layers and play the role of tetrahedra with the Pb-lone-pair as the forth apex. Crystal chemical comparison revealed similarities and differences with the classical structure type of α-celsian Ba[Al₂Si₂O₈] with the tetrahedral double layer. Recently investigated nonlinear optical acentric borates Pb₂(BO₃)(NO₃) and Pb₂(BO₃)Cl are both related to this structural type, possessing umbrella-like groups [PbO₃]^4- and honeycomb layers [Pb₂(BO₃)]⁺ with the BO₃-triangles on the tetrahedral positions.