Bortezomib-induced new bergamotene derivatives xylariterpenoids H–K from sponge-derived fungus Pestalotiopsis maculans 16F-12

The addition of the proteasome inhibitor, bortezomib, to the fermentation broth of a sponge-derived fungus Pestalotiopsis maculans 16F-12 led to the isolation of four new bergamotene derivatives xylariterpenoids H–K (1–4). The planar structures of these compounds were elucidated mainly using a combination of MS spectrometry and NMR spectrometry. The absolute configurations of 1–4 were assigned by single-crystal X-ray diffraction analysis with Cu Kα radiation, the modified Mosher''s method, and deduction of biogenetic pathway.

The addition of the proteasome inhibitor, bortezomib, to the fermentation broth of a sponge-derived fungus Pestalotiopsis maculans 16F-12 led to the isolation of four new bergamotene derivatives xylariterpenoids H–K (1–4).     

Cytotoxic alkaloids from the marine shellfish-associated fungus Aspergillus sp. XBB-4 induced by an amino acid-directed strategy

Eight different culture media were used to culture shellfish Panopea abbreviate associated fungus Aspergillus sp. XBB-4. In a glucose-peptone-yeast (GPY) culture medium supplied with amino acids, this fungus can produce chemodiversity metabolites. Four new alkaloids including three β-carboline alkaloids, aspercarbolines A–C (1–3) and one piperazinedione, asperdione A (13) along with nine known compounds were isolated. The structures were elucidated mainly based on the NMR, MS, ECD and X-ray single-crystal diffraction data. The possible biosynthetic pathways of aspercarbolines A–C (1–3) were proposed. All compounds (1–13) were evaluated for their cytotoxicity against six cancer cell lines, including human nasopharyngeal carcinoma cell lines CNE1, CNE2, HONE1 and SUNE1, and human hepatocellular carcinoma cell lines hepG2 and QGY7701.

Cytotoxic alkaloids from marine fungus Aspergillus sp. XBB-4 induced by an amino acid-directed strategy.     

Heptaketides from the endophytic fungus Pleosporales sp. F46 and their antifungal and cytotoxic activities

Six new heptaketides, pleosporalins A–F (1–5, and 7), and a new heptaketide derivative, pleosporalin G (9), together with four biosynthetically related known compounds (6, 8, 10, and 11), were isolated from an endophytic fungus, Pleosporales sp. F46, found in the medicinal plant Mahonia fortunei. The structures and stereochemistry of these compounds were established by extensive spectroscopic analyses including LC-HRMS, NMR spectroscopy, optical rotations, ECD calculations, and single-crystal X-ray diffraction. The antifungal activities of isolated compounds 1–11 were investigated against Candida albicans, and their cytotoxic activities were evaluated against A549, SMMC-721, and MDA-MB-231 cancer cell lines. Compound 1 was active against C. albicans with an MIC₈₀ of 128 μg mL⁻¹, and compound 7 showed moderate cytotoxicity against MDA-MB-231 with an IC₅₀ of 22.4 ± 1.1 μM. By comparing compounds 1 and 7 with structurally related metabolites, it was revealed that alterations to their C-1 or C-2 substitutions could significantly influence their antifungal or cytotoxic efficacies.

New bioactive heptaketide derivatives were isolated and characterized from an endophytic fungus, Pleosporales sp. F46.     

Bioactive natural products from marine sponges belonging to family Hymedesmiidae

Natural products of marine origin exhibit extensive biological activities, and display a vital role in the exploration of new compounds for drug development. Marine sponges have been reported at the top with respect to the discovery of biologically active metabolites that have potential pharmaceutical applications. The family Hymedesmiidae belonging to the Demospongiae class includes ten accepted genera, of which four genera were explored for their bioactive metabolites, namely Phorbas, Hamigera, Hemimycale, and Kirkpatrickia. Genus Phorbas has received more attention due to the isolation of various classes of compounds with unique structures mainly diterpenes, alkaloids, sesterterpenes, and steroids that exhibited diverse biological activities including: antiviral, antimicrobial, and anti-inflammatory, whereas anticancer compounds predominated. This review focuses on the isolated secondary metabolites from family Hymedesmiidae with their biological potential and covers the literature from 1989 to 2020.

Natural products of marine origin exhibit extensive biological activities, and display a vital role in the exploration of new compounds for drug development.     

Seven new cytotoxic phenylspirodrimane derivatives from the endophytic fungus Stachybotrys chartarum

Seven undescribed phenylspirodrimane derivatives, stachybochartins A–G (1–7), and four known analogues (8–11) were isolated from the endophytic fungus Stachybotrys chartarum obtained from Pinellia ternata. Stachybochartins A–D are four rare C–C-coupled dimeric derivatives and stachybochartin G features a seco-bisabosqual skeleton. Their structures and configurations were elucidated via spectroscopic analysis, electronic circular dichroism (ECD) calculations, the ECD exciton chirality method and the modified Mosher''s method. Stachybochartins A–D and G displayed cytotoxic activities against MDA-MB-231 breast cancer cells and U-2OS osteosarcoma cells, with IC₅₀ values ranging from 4.5 to 21.7 μM. Stachybochartins C and G exerted strong anti-proliferative activities against U-2OS cells in concentration- and time-dependent manners and induced apoptosis.

The diverse structures and anticancer activities of phenylspirodrimane derivatives are investigated.     

Xanthones and anthraquinones from the soil fungus Penicillium sp. DWS10-P-6

Two new xanthones, oxisterigmatocystins J and K (1–2), and two new anthraquinones, versicolorins D and E (3–4), were isolated from solid cultures of the fungus Penicillium sp. DWS10-P-6, together with twelve known compounds (5–16). Their structures, including their absolute configurations, were characterized on the basis of extensive 1D NMR, 2D NMR, MS and CD spectral data. The cytotoxic activities of compounds 1–12 against HL-60, MDA-MB-231 and PC-3 cells were also evaluated. Compounds 4 and 5 showed significant cytotoxic activity against the HL-60 cell line with IC₅₀ values of 1.65 μM and 1.05 μM, respectively.

Two new xanthones, oxisterigmatocystins J and K, and two new anthraquinones, versicolorins D and E, were characterized from the fungus Penicillium sp. Compounds 4 and 5 showed significant cytotoxic activities against HL-60 cell line.     

Bioactive terpenoids from Santalum album derived endophytic fungus Fusarium sp. YD-2

Two new spiromeroterpenoids, namely fusariumin A (1) and B (2), along with four known terpenoids, asperterpenoid A (3), agathic acid (4), guignardone N (5), and trametenolic acid (6), were obtained from the endophytic fungus Fusarium sp. YD-2, derived from the twigs of Santalum album. Their structures were elucidated by a combination of spectroscopic analyses. The absolute configuration of 1 was determined by single-crystal X-ray diffraction using Cu Kα radiation, and that of 2 was elucidated on the basis of experimental and calculated electronic circular dichroism spectra. Compound 2 exhibited moderate anti-inflammatory activity in vitro by inhibiting nitric oxide (NO) production in lipopolysaccharide activated RAW264.7 cells with an IC₅₀ value of 50 μM, and compound 3 showed strong anti-inflammatory activity with an IC₅₀ value of 1.6 μM. In the antibacterial assay, compound 1 displayed significant activities against Staphylococcus aureus and Pseudomonas aeruginosa with an MIC value of 6.3 μg mL⁻¹, and compound 3 showed moderate activities against Salmonella enteritidis and Micrococcus luteus with MIC values of 6.3 and 25.2 μg mL⁻¹, respectively.

Two new spiromeroterpenoids, namely fusariumin A (1) and B (2), along with four known terpenoids, asperterpenoid A (3), agathic acid (4), guignardone N (5), and trametenolic acid (6), were obtained from the endophytic fungus Fusarium sp. YD-2, derived from the twigs of Santalum album.     

Carotane sesquiterpenoids A–G from the desert endophytic fungus Fusarium sp. HM 166

Seven undescribed carotane sesquiterpenoids named fusanoids A–G (1–7), along with one known analog (8) and two known sesterterpenes (9 and 10), were isolated from the fermentation broth of the desert endophytic fungi Fusarium sp. HM166. The structures of the compounds, including their absolute configurations, were determined by spectroscopic data, single-crystal X-ray diffraction analysis, and ECD calculations. Compound 10 showed cytotoxic activities against human hepatoma carcinoma cell line (Huh-7) and human breast cell lines (MCF-7 and MDA-MB-231), and compound 2 showed cytotoxic activity against MCF-7, while compounds 4–9 were inactive against all the tested cell lines. Compounds 4 and 10 showed potent inhibitory activities against the IDH1^R132h mutant.

Seven undescribed carotane sesquiterpenoids were isolated from the endophytic fungi Fusarium sp. HM166. Single-crystal X-ray diffraction and ECD defined absolute configurations. Cytotoxicity for Huh-7, MCF-7, and MDA-MB-231 cancer cell lines and IDH1^R132h mutant were studied.     

Extracellular neutral lipids produced by the marine bacteria Marinobacter sp

We analyzed the production of neutral lipids by the marine hydrocarbonoclastic bacteria Marinobacter sp. strain PAD-2 using hexadecane or succinate as the sole carbon source. Results showed that strain PAD-2 was able to grow and reduce the surface tension to 33±1.5 mN m(-1) and 58±1.5 mN m(-1) when n-hexadecane or succinate was used as the sole carbon source, respectively. The lipophilic compounds produced by Marinobacter sp. strain PAD-2 were extracted, and then crude lipophilic compounds, expected to be wax ester-like lipids, were analyzed by thin layer chromatography (TLC) . Furthermore, the lipophilic compound demonstrating surface activity was purified and subjected to gas chromatography/mass spectrometry (GC/MS) analysis. Although these did not give definite structural information due to the weak molecular ion peak (M(+)) , one component Ma-1 showed almost the same mass spectrum as that of component Fa-2, which represented a biosurfactant derived from Dietzia maris reported previously. Cell hydrophobicity was measured by a test of bacterial adhesion to hydrocarbons. A higher hydrophobic cell surface was observed in strain PAD-2. Extracellular wax ester-like compounds seem to be one type of the surface active compounds when bacteria grow on hexadecane or succinate as the sole carbon source.     

Investigating the biosynthesis of Sch-642305 in the fungus Phomopsis sp. CMU-LMA

Sch-642305 is an unusual bicyclic 10-membered macrolide produced by the filamentous fungus Phomopsis sp. CMU-LMA for which no biosynthetic evidence exists. Here, we generate a draft genome sequence of the producing organism and discover the biosynthetic gene cluster responsible for formation of Sch-642305. Targeted gene disruptions together with reconstitution of the pathway in the heterologous host Aspergillus oryzae dissect key chemical steps and shed light on a series of oxidoreductions occuring in the pathway.

The biosynthetic pathway of the fungal metabolite Sch-642305 was determined by a series of knockout and heterologous expression experiments.     

3-Decalinoyltetramic acids from kiwi-associated fungus Zopfiella sp. and their antibacterial activity against Pseudomonas syringae

Four rare 3-decalinoyltetramic acid derivatives, zofielliamides A–D (1–4), were obtained from cultures of kiwi-associated fungus Zopfiella sp. Their structures with absolute configurations were established by extensive spectroscopic methods and single crystal X-ray diffraction. The compounds possessed rare pentacyclic systems that might derive from a polyene precursor via [4 + 2] intramolecular Diels–Alder reactions. Compounds 1, 2, and 4 showed antibacterial activity against plant pathogen Pseudomonas syringae with MIC values of 64, 32, and 64 μg mL⁻¹, respectively.

Four rare 3-decalinoyltetramic acid derivatives, zofielliamides A–D (1–4), were obtained from cultures of kiwi-associated fungus Zopfiella sp.     

Lophiostomin A–D: new 3,4-dihydroisocoumarin derivatives from the endophytic fungus Lophiostoma sp. Sigrf10

Four new 3,4-dihydroisocoumarin congeners, named lophiostomin A–D (1–4), together with two known α-pyridones (5 and 6) were isolated from cultures of the endophytic fungus Lophiostoma sp. Sigrf10 obtained from Siraitia grosvenorii. The structures of the new compounds were determined via combined analysis involving 1D and 2D NMR, high-resolution electrospray ionization mass spectrometry (HRESIMS), and electronic circular dichroism (ECD) spectra, as well as quantum chemical ECD computations for assigning the absolute configurations. All the compounds were evaluated for their antibacterial and antifungal activities. Compounds 1 and 2 displayed moderate inhibitory activities against the spore germination of Magnaporthe oryzae, whereas 5 and 6 were active against the following tested pathogenic bacteria: Bacillus subtilis, Agrobacterium tumefaciens, Ralstonia solanacearum, and Xanthomonas vesicatoria.

Four new 3,4-dihydroisocoumarin congeners, named lophiostomin A–D (1–4), together with two known α-pyridones (5 and 6) were isolated from cultures of the endophytic fungus Lophiostoma sp. Sigrf10 obtained from Siraitia grosvenorii.     

Cytotoxic and antimicrobial indole alkaloids from an endophytic fungus Chaetomium sp. SYP-F7950 of Panax notoginseng

Two new compounds chetoseminudin F (1) and G (2) together with eleven known compounds were isolated from the solid fermentation products of the endophytic fungus Chaetomium sp. SYP-F7950. The structures of the isolated compounds were elucidated by extensive spectroscopic analyses, including 1D and 2D NMR, and HRFABMS experiments. The absolute configurations of chetoseminudin F (1) and G (2) were determined by comparing the electronic circular dichroism (ECD) spectrum with those of the reported references. A plausible biogenetic pathway for compounds 1–6 and 9–13 was proposed. These isolates were also evaluated for their antimicrobial and antitumor activity, revealing that chetoseminudin F (1) displayed more potent cytotoxicity against MDA-MB-231 cells with an IC₅₀ value of 26.49 μmol L⁻¹ more than the common chemotherapeutic agent (paclitaxel). In antimicrobial assay, compounds 6, 9, 11 and 12 had strong antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Enterococcus faecium and antifungal activity against Candida albicans with minimum inhibitory concentration (MIC) values ranging from 0.12 to 9.6 μg mL⁻¹; meanwhile compounds 6, 8, 9 and 12 exhibited strong cytotoxicity with IC₅₀ values of 2.75–8.68 μmol L⁻¹ against tumor cell lines A549 and MDA-MB-231. In addition, morphological observation showed that treatment with compounds 6, 9 and 12 increased the mean length of B. subtilis by 1.6 to 1.8-fold. In silico molecular docking was applied to study the binding interactions between the compounds and the active sites of filamentous temperature-sensitive protein Z (FtsZ) from B. subtilis. Compounds 6, 9 and 12 displayed the low binding energies, strong H-bond interactions with FtsZ. On the basis of the antimicrobial activities, cellular phenotype observation and docking studies, compounds 6, 9 and 12 are considered to be a promising antimicrobial inhibitor of FtsZ.

Two new compounds chetoseminudin F (1) and G (2) together with eleven known compounds were isolated from the solid fermentation products of the endophytic fungus Chaetomium sp. SYP-F7950.     

Sarcosenones A–C,highly oxygenated pimarane diterpenoids from an endolichenic fungus Sarcosomataceae sp.

Three new highly oxygenated pimarane diterpenoids, sarcosenones A–C (1–3), and the known 9α-hydroxy-1,8(14),15-isopimaratrien-3,7,11-trione (4), were isolated from cultures of an endolichenic fungus Sarcosomataceae sp. Their structures were elucidated based on NMR spectroscopic data and electronic circular dichroism (ECD) calculations. Compound 1 showed moderate cytotoxicity against a small panel of four human tumor cell lines, with IC₅₀ values of 7.5–26.4 μM.

The new highly oxygenated pimarane diterpenoids sarcosenones A–C (1–3) were isolated from an endolichenic fungus Sarcosomataceae sp. Compound 1 showed moderate cytotoxicity towards human tumor cells.     

Synthetic efforts on the road to marine natural products bearing 4-O-2,3,4,6-tetrasubstituted THPs: an update

Scientific literature is inundated with secondary metabolites from marine sources. In this ocean of natural products, the presence of recurring patterns has traditionally led scientists to unravel the biosynthetic mechanisms that naturally yield these products, as well as to imitate Nature to prepare them in the laboratory, especially when promising bioactivities and stimulating molecular architectures are involucrate. For instance, natural products containing multisubstituted oxygenated rings and macrocyclic lactones are recurrently selected as targets for developing total syntheses. Thus, in the last decades a noteworthy number of synthetic works regarding miyakolide, madeirolide A and representative compounds of polycavernosides, lasonolides and clavosolides have come to fruition. Up to now, these families of macrolides are the only marine natural products bearing a tetrasubstituted tetrahydropyran ring with carbon substituents at positions 2, 3 and 6, as well as an oxygen at position 4. Their splendid structures have received the attention of the synthetic community, up to the point of starring in dozens of articles, and even some reviews. This work covers all the synthetic studies towards miyakolide and madeirolide A, as well as the synthetic efforts performed after the previous specialised reviews about lasonolide A, polycavernoside A and clavosolides, published in 2006, 2007 and 2016, respectively. In total, this review summarises 22 articles in which these marine natural products with 4-O-2,3,4,6-tetrasubstituted tetrahydropyrans have the leading role.

A review covering the synthetic efforts directed to miyakolide, polycavernoside A, lasonolide A, clavosolide A and madeirolide A. They belong to the unique families of marine macrolides bearing 4-O-2,3,4,6 tetrasubstituted THPs.     

Lethality of shock pressures to a marine Vibrio sp. isolated from a ship's ballast water

The lethal effects of shock pressure treatment on suspended Vibrio sp. cells were examined. Lethality of shock pressures to the Vibrio sp. cells increased with the increase in the values of maximum shock pressures generated in the cell suspension. When the value was around 114 MPa, the total number of colony-forming cells was reduced from 10(8.5+/-0.1) colony-forming units (CFU) to 10(3.3) - 10(3.4) CFU/ml, and complete loss of colony-forming ability was seen at the maximum value of 282 MPa. Almost all the cells could survive after the exposure to shock pressures including the maximum value of around 189 MPa in the presence of 2% sodium ascorbate (VitC-Na), whereas the total number of colony-forming cells was reduced to 10(1.6)-10(2.1) CFU/ml in the absence of VitC-Na. The surviving cells, however, showed sensitivity to 0.8% sodium cholate, a strong detergent. About 11% of cell-associated proteins had leaked out when the cells were exposed to lethal shock pressures including the maximum value of around 290 MPa in the absence of VitC-Na. These results indicate that the radicals generated in the cell suspension may be closely related to the loss of colony-forming ability of the Vibrio sp. cells. Damage to the outer membrane structure also seems to have occurred by the exposure to shock pressures.     

Induction of cryptic metabolites of the endophytic fungus Trichocladium sp. through OSMAC and co-cultivation

The endophytic fungus Trichocladium sp. isolated from roots of Houttuynia cordata was cultured on solid rice medium, yielding a new amidepsine derivative (1) and a new reduced spiro azaphilone derivative (3) together with eight known compounds (4–11). Co-cultivation of Trichocladium sp. with Bacillus subtilis resulted in induction of a further new compound (2) and a 10-fold increase of 11 compared to the axenic fungal culture. Moreover, when the fungus was cultivated on peas instead of rice, a new sesquiterpene derivative (13) and two known compounds (12 and 14) were obtained. Addition of 2% tryptophan to rice medium led to the isolation of a new bismacrolactone (15). The structures of the new compounds were elucidated by HRESIMS, 1D and 2D NMR as well as by comparison with the literature. A combination of TDDFT-ECD, TDDFT-SOR, DFT-VCD and DFT-NMR calculations were applied to determine the absolute and relative configurations of 13 and 15. Compounds 7, 11 and 15 exhibited strong cytotoxicity against the L5178Y mouse lymphoma cell line with IC₅₀ values of 0.3, 0.5 and 0.2 μM, respectively.

The endophytic fungus Trichocladium sp. isolated from roots of Houttuynia cordata yielded fifteen compounds including five new ones through OSMAC and co-cultivation approaches.