Integrating Activity-Guided Strategy and Fingerprint Analysis to Target Potent Cytotoxic Brefeldin A from a Fungal Library of the Medicinal Mangrove Acanthus ilicifolius.

Mangrove-associated fungi are rich sources of novel and bioactive compounds. A total of 102 fungal strains were isolated from the medicinal mangrove Acanthus ilicifolius collected from the South China Sea. Eighty-four independent culturable isolates were identified using a combination of morphological characteristics and internal transcribed spacer (ITS) sequence analyses, of which thirty-seven strains were selected for phylogenetic analysis. The identified fungi belonged to 22 genera within seven taxonomic orders of one phyla, of which four genera Verticillium, Neocosmospora, Valsa, and Pyrenochaeta were first isolated from mangroves. The cytotoxic activity of organic extracts from 55 identified fungi was evaluated against human lung cancer cell lines (A-549), human cervical carcinoma cell lines (HeLa), human hepatoma cells (HepG2), and human acute lymphoblastic leukemia cell lines (Jurkat). The crude extracts of 31 fungi (56.4%) displayed strong cytotoxicity at the concentration of 50 µg/mL. Furthermore, the fungus Penicillium sp. (HS-N-27) still showed strong cytotoxic activity at the concentration of 25 µg/mL. Integrating cytotoxic activity-guided strategy and fingerprint analysis, a well-known natural Golgi-disruptor and Arf-GEFs inhibitor, brefeldin A, was isolated from the target active strain HS-N-27. It displayed potential activity against A549, HeLa and HepG2 cell lines with the IC50 values of 101.2, 171.9 and 239.1 nM, respectively. Therefore, combining activity-guided strategy with fingerprint analysis as a discovery tool will be implemented as a systematic strategy for quick discovery of active compounds.

Design, Semisynthesis, Insecticidal and Antibacterial Activities of a Series of Marine-Derived Geodin Derivatives and Their Preliminary Structure-Activity Relationships.

To enhance the biological activity of the natural product geodin (1), isolated from the marine-derived fungus Aspergillus sp., a series of new ether derivatives (2-37) was designed and semisynthesized using a high-yielding one-step reaction. In addition, the insecticidal and antibacterial activities of all geodin congeners were evaluated systematically. Most of these derivatives showed better insecticidal activities against Helicoverpa armigera Hübner than 1. In particular, 15 showed potent insecticidal activity with an IC50 value of 89 µM, comparable to the positive control azadirachtin (IC50 = 70 µM). Additionally, 5, 12, 13, 16, 30 and 33 showed strong antibacterial activity against Staphylococcus aureus and Aeromonas salmonicida with MIC values in the range of 1.15-4.93 µM. The preliminary structure-activity relationships indicated that the introduction of halogenated benzyl especially fluorobenzyl, into 1 and substitution of 4-OH could be key factors in increasing the insecticidal and antibacterial activities of geodin.

Aspersymmetide A, a New Centrosymmetric Cyclohexapeptide from the Marine-Derived Fungus Aspergillus versicolor.

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.

Structure modification, antialgal, antiplasmodial, and toxic evaluations of a series of new marine-derived 14-membered resorcylic acid lactone derivatives.

Marine natural products play critical roles in the chemical defense of many marine organisms and are essential, reputable sources of successful drug leads. Sixty-seven 14-membered resorcylic acid lactone derivatives 3-27 and 30-71 of the natural product zeaenol (1) isolated from the marine-derived fungus Cochliobolus lunatus were semisynthesized by chlorination, acylation, esterification, and acetalization in one to three steps. The structures of these new derivatives were established by HRESIMS and NMR techniques. All the compounds (1-71) were evaluated for their antialgal and antiplasmodial activities. Among them, 14 compounds displayed antifouling activities against adhesion of the fouling diatoms. In particular, 9 and 34 exhibited strong and selective inhibitory effects against the diatoms Navicula laevissima and Navicula exigua (EC50 = 6.67 and 8.55 µmol/L), respectively, which were similar in efficacy to those of the positive control SeaNine 211 (EC50 = 2.90 and 9.74 µmol/L). More importantly, 38, 39, and 69-71 showed potent antiplasmodial activities against Plasmodium falciparum with IC50 values ranging from 3.54 to 9.72 µmol/L. Very interestingly, the five antiplasmodial derivatives displayed non-toxicity in the cytotoxicity assays and the zebrafish embryos model, thus, representing potential promising antiplasmodial drug agents. The preliminary structure-activity relationships indicated that biphenyl substituent at C-2, acetonide at positions C-5' and C-6', and tri- or tetra-substituted of acyl groups increased the antiplasmodial activity. Therefore, combining evaluation of chemical ecology with pharmacological models will be implemented as a systematic strategy, not only for environmentally friendly antifoulants but also for structurally novel drugs. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-021-00103-0.

Design, semisynthesis, α-glucosidase inhibitory, cytotoxic, and antibacterial activities of p-terphenyl derivatives.

Terphenyllin (1), a naturally abundant p-terphenyl metabolite, was isolated from the coral derived fungus Aspergillus candidus together with four natural analogues 2-5. To evaluate their potency and selectivity, a series of new derivatives of 1 were designed and semisynthesized. They were evaluated for their α-glucosidase inhibitory, cytotoxic, and antibacterial activities. Compounds 1, 3, 4, 7, 8, 10, 11, 14, 15, 21, 23, 24, 29, 39, and 40 showed significant α-glucosidase inhibitory activity with IC50 values of 4.79-15 µM, which were stronger than that of the positive controls, 1-deoxynojirimycin (IC50 = 192.0 µM) and acarbose (IC50 = 707.9 µM). Compounds 7 and 10 have relatively higher therapeutic indices (CC50/IC50 = 17 and 10, respectively), representing potential promising leads. The enzyme kinetic studies of compounds 1 and 24 showed a non-competitive inhibition on α-glucosidase with Ki values of 1.50 and 3.45 µM, respectively. Additionally, compounds 14, 21, 26, 29, 32, 35, and 37 were found to exhibit strong cytotoxicity against three tumor cell lines A549 (lung adenocarcinoma epithelial), HeLa (cervical carcinoma), and HepG2 (hepatocellular liver carcinoma) with IC50 values ranging from 0.15 to 5.26 µM. Further study indicated that 32 could induce S-phase arrest in the cell cycle progression.

[Characteristics and Mechanism of Copper Adsorption from Aqueous Solutions on Biochar Produced from Sawdust and Apple Branch].

In order to utilize the waste biomass resources efficiently, two raw materials of sawdust and apple branch were selected to produce biochars at 450℃ by oxygen-limited pyrolysis, and the adsorptions of Cu2+ in aqueous solutions were evaluated. The effects of initial Cu2+ concentration and contact time in batch sorption experiments were investigated by the four kinds of isothermal adsorption models (Langmuir, Freundlich, Temkim, D-R model) and the four kinds of adsorption kinetics models (Pseudo first-order, Pseudo second-order, Elovich model, Intraparticle diffusion model). The influencing factors of adsorption characteristics about sawdust biochar (JB) and apple branch biochar (PB) were discussed by characterizing their elemental composition, functional groups, surface area, surface morphology and scanning electron microscope. The results showed that:1The adsorption equilibrium of PB and JB was reached in three hours and six hours, respectively, and the maximum adsorption capacity of PB and JB reached 15.85 mg·g-1 and 17.44 mg·g-1, respectively. Compared with other studies, these biochars showed higher Cu2+ adsorption performance. 2The adsorption kinetics was best fitted by the pseudo-second order model, while the isothermal adsorption was best described by Langmuir isotherms. This indicated that the beneficial adsorption process via monolayer was affected by intraparticle diffusion, surface adsorption and liquid film diffusion. 3The adsorption mechanism for Cu2+ is a complex interaction of physical and chemical factors. Electrostatic interaction of physical adsorption is mainly adsorption mechanism, Chemical adsorption mechanism includes generally ligand exchange (phenolic hydroxyl)/ion exchange (H+) and cationic-π. It was demonstrated that JB and PB could be considered as promising materials to immobilize heavy metals in contaminated water or soil.

Aspergivones A and B, two new flavones isolated from a gorgonian-derived Aspergillus candidus fungus.

Two new flavones, aspergivones A (1) and B (2), were isolated from the fungus Aspergillus candidus cultured from the gorgonian coral Anthogorgia ochracea collected from the South China Sea. The structures of 1 and 2 were elucidated by NMR and MS methods and comparison with relatively known compounds. Only 2 showed slight inhibitory activity against alpha-glucosidase with an IC50 value of 244 µg/mL. Compounds 1 and 2 were also evaluated for their cytotoxic and antibacterial activities.

[Effect of Biochar on Soil Greenhouse Gas Emissions in Semi-arid Region].

This study aimed to investigate the effects of biochar addition on the emission of greenhouse gases from farmland soil in semi-arid region. Through an in-situ experiments, the influence of sawdust biochar(J) and locust tree skin biochar (H) at three doses (1%, 3%, and 5% of quality percentage) on C2, CH4 and N2O emissions were studied within the six months in the south of Ningxiaprovince. The results indicated that soil CO2 emission flux was slightly increased with the addition doses for both biochars, and the averaged CO2 emission flux for sawdust and locust tree skin biochar was enhanced by 1. 89% and 3. 34% compared to the control, but the difference between treatments was not statistically significant. The soil CH4 emission was decreased with the increasing of biochar doses, by 1. 17%, 2. 55%, 4. 32% for J1, J3, J5 and 2. 35%, 5. 83%, 7. 32% for H1, H3, H5, respectively. However, the difference was statistically significant only for J5, H3 and H5 treatments (P <0. 05). Across addition doses, there was no apparent effect on soil N2O emission. Our study indicated that the biochar has no significant influence on soil CO2 and N2O emissions within six months in semi-arid region and can significantly influence soil CH4 emissions (P < 0. 05). As for biochar type, the locust tree skin biochar is significantly better than the sawdust biochar in terms of restraining CH4 emission(P = 0. 048).

[Effects of biochar addition into soils in semiarid land on water infiltration under the condition of the same bulk density].

Making clear the effects of biochar addition on soil water infiltration process can provide the scientific basis for the evaluation of the influence of biochar application on soil hydrology in semi-arid region. In this paper, through the soil column simulation method in laboratory, the effects of biochar of three sizes (1-2 mm, 0.25-1 mm and ≤ 0.25 mm) at 4 doses (10, 50, 100 and 150 g x kg(-1)) on the cumulative infiltration, the permeability and the stable infiltration rate of two different soils (anthrosol and aeolian sandy soil) were studied. The results showed that the infiltration capacity of the anthrosol was obviously increased compared to the control, however, the one in the aeolian sandy soil was decreased due to the biochar addition. At 100 minutes after infiltration starting, the averaged cumulative infiltration was increased by 25.1% in the anthrosol with comparison to the control. Contrarily, the averaged cumulative infiltration was decreased by 11.1% in the aeolian sandy soil at 15 minutes after infiltration starting. When the dose was the same, biochar with different particle sizes improved the infiltration for the anthrosol, but for the different dose treatments, the particle size of biochar which showed the greatest improvement was different. As for the aeolian sandy soil, the infiltration increased at the dose of 10 g x kg(-1) after the addition of biochar with different particle sizes, while decreased at the higher dose of 50, 100 and 150 g x kg(-1). The cumulative infiltration of the aeolian sandy soil was decreased with the increase in addition amount of biochar with the same particle size, while it was not so for the anthrosol. The determination coefficient fitted by the Philip infiltration model ranged from 0.965 to 0.999, suggesting this model was suitable for the simulation of soil water infiltration process after biochar application. Statistical analysis of main effects showed that the biochar particle size, the biochar addition amount, and the interactive effect had statistically significant effect on the soil permeability and stable infiltration rate in the two soils. In conclusion, the biochar had different effects on the soils with different textures, moreover, there was a positive correlation relationship between the impact and the addition amount.