Napyradiomycin A4 and Its Relate Compounds, a New Anti-PRV Agent and Their Antibacterial Activities, from Streptomyces kebangsaanensis WS-68302.

Two new napyradiomycins derivatives, napyradiomycin A4 (1) and A80915 H (2), along with five known ones, were isolated from the ethyl acetate extract of fermentation culture of Streptomyces kebangsaanensis WS-68302. Their structures were elucidated by extensive spectroscopic analysis, including HR-MS, 1D and 2D NMR, CD spectrum, as well as comparison with literature data. Compound 1 exhibited significant antiviral activity against PRV (Pseudorabies virus) with an IC50 value of 2.056 µM and therapeutic ratio at 14.98, suggesting that it might have potential for development of an antiviral agent. Moreover, compound 1 displayed the strongest inhibition against PRV protein among the tested napyradiomycins in the indirect immunofuorescence assay. Compounds 3 and 4 showed higher activities against swine pathogenic Streptococcus suis than the positive control penicillin G sodium salt, with MIC values of 3.125 and 6.25 µg/mL, respectively. Compounds 1 and 3-6 exhibited moderate antibacterial activity against the swine pathogenic Erysipelothrix rhusiopathiae, with MIC values ranging from 25 to 50 µg/mL.

Antiviral Activity of Benzoheterocyclic Compounds from Soil-Derived Streptomyces jiujiangensis NBERC-24992

Pseudorabies virus (PRV) is a pathogen that causes Aujeszky's disease (AD) in animals, leading to huge economic losses to swine farms. In order to discover anti-PRV compounds, we studied the extracts of the strain Streptomyces jiujiangensis NBERC-24992, which showed significant anti-PRV activity. Eight benzoheterocyclic secondary metabolites, including three new compounds (1-3, virantmycins D-G) and five known compounds (4-8, virantmycin, A-503451 D, A-503451 D acetylate, A-503451 A, and A-503451 B), were isolated from the broth of NBERC-24992. The structures of the new compounds were identified by using extensive spectroscopic data, including mass spectrometry (MS), nuclear magnetic resonance (NMR), and electronic circular dichroism (ECD). Compound 1 was found to be a novel heterocyclic compound with a tricyclic skeleton from natural product. All compounds were tested for antiviral activity, and 4 (virantmycin) showed an excellent effect against PRV and was better than ribavirin and acyclovir. Our study revealed that chlorine atom and tetrahydroquinoline skeleton were important active moiety for antiviral activity. Virantmycin could be a suitable leading compound for an antiviral drug against PRV.

Selective and effective anticancer agents: Synthesis, biological evaluation and structure-activity relationships of novel carbazole derivatives.

Carbazole alkaloids is an important class of natural products with diverse biological functions. So, the aim of this article is to explore new chemical entities containing carbazole scaffold as potential novel cytotoxic agents based on our developed three-component indole-to-carbazole reaction. Two series of carbazole derivatives were designed and synthesized, and their in vitro cytotoxic activities against three cell lines (A875, HepG2, and MARC145) were evaluated. The results indicated that some of these carbazole derivatives exhibited significantly good cytotoxic activities against tested cell lines compared with the control 5-fluorouracil (5-FU). Especially, carbazole acylhydrazone compounds 7g and 7p displayed high inhibitory activity on cancer cells, but almost no activity on normal cells. Further analysis of induced apoptosis for potential compounds indicated that the potential antitumor agents induced cell death in A875 cells at least partly (initially) by apoptosis, which might be used as promising lead scaffold for discovery of novel carbazole-type cytotoxic agents.

Sulfur-containing natural hinduchelins derivatives as potential antifungal agents against Rhizoctonia solani.

Aryl-oxazole alkaloids are an important class of heterocyclic natural products, and which has been demonstrated to exhibit broad biological functions. During the course of our research for highly active compounds from natural products, the natural hinduchelins A-D with typical aryl-oxazole unit have been synthesized and investigated. So, in order to develop highly potential functional molecules, a series of novel sulfur-containing aryl-oxazole compounds derived from natural hinduchelins was designed and synthesized, and their in vitro fungicidal activities against four common plant pathogenic fungi (oomycetes Phytophthora capsici, ascomycetes Sclerotinia sclerotiorum, deuteromycetes Botrytis cinerea and basidiomycetes Rhizoctonia solani) were evaluated, the results demonstrated that compounds 7b and 7c displayed good selectivity and specificity in vitro against basidiomycetes R. solani. In addition, the in vivo antifungal activities also indicated compounds 7b and 7c can protect the horsebean against infection by R. solani, and the possible mechanism of antifungal action for these compounds has also been investigated.

An efficient synthesis and bioactivity evaluation of oxazole-containing natural hinduchelins A-D and their derivatives.

Oxazoles are an important class of biologically active metabolites from nature, and exhibit broad biological activities as the lead for drug discovery. Hinduchelins are a class of unusual natural products with an oxazole unit, isolated from Streptoalloteichus hindustanus, and with a potential iron-chelating ability. These compounds are the first identified naturally occurring unusual oxazole derivatives to possess a catechol unit. However, some of these compounds are not abundant in nature, and thus, the efficient syntheses of these compounds are advantageous in exploring their potential applications. This paper reports the efficient synthesis and bio-evaluation of hinduchelins A-D and their derivatives with convenient procedures and high yields.

Synthesis and bioevaluation of novel steroidal isatin conjugates derived from epiandrosterone/androsterone.

Steroids are classes of natural products widely distributed in nature, which have been demonstrated to exhibit broad biological functions, and have also attracted increasing interest from bioorganic and pharmaceutical researches. In order to develop novel chemical entities as potential cytotoxic agents, a series of steroidal isatin conjugations derived from epiandrosterone and androsterone were efficiently prepared and characterized, and all these obtained compounds were screened for their potential cytotoxic activities. The preliminary bioassay indicated that most of the newly synthesized compounds exhibited good cytotoxic activities against human gastric cancer (SGC-7901), melanoma (A875), and hepatocellular liver carcinoma (HepG2) cell lines compared with 5-fluorouracil (5-FU), which might be considered as promising scaffold for further development of potential anticancer agents.

Silencing forkhead box M1 promotes apoptosis and autophagy through SIRT7/mTOR/IGF2 pathway in gastric cancer cells.

Forkhead box M1 (FOXM1) was initially identified as an oncogenic transcription factor, and multiple lines of evidence have demonstrated that FOXM1 is abundantly expressed and plays an irreplaceable role in several types of human cancers. Also, evidence has shown the association of FOXM1 with gastric carcinoma metastasis and patients prognosis; however, the potential role and molecular mechanism of FOXM1 in gastric cancer cell apoptosis are still obscure. The current study indicates that FOXM1 is highly expressed in a variety of gastric carcinoma cell lines, such as BGC823, MGC803, AGS, and SGC-7901, compared with the normal gastric mucosal epithelial cell lines CES-1. FOXM1 silence markedly inhibits AGS and SGC-7901 cell survival and proliferation, increases their apoptosis, and modulates apoptosis-related protein expression, including reduced Bcl-2 level and increased Bax and caspase-3 levels. Further study showed that FOXM1 depletion induced cell autophagy through increasing the level of beclin-1 and decreasing the P62 expression. We next corroborated that FOXM1 silence abolished the expression of Sirtuin 7 (SIRT7) and increased the level of insulin-like growth factor 2 (IGF2) and mammalian target of rapamycin (mTOR). Finally, our data documented that the SIRT7/mTOR/IGF2 pathway was involved in the function of FOXM1 in AGS cell growth and apoptosis. In conclusion, these results confirmed that FOXM1 is involved in gastric carcinoma progression via the SIRT7/mTOR/IGF2 pathway.

Highly Sensitive Dual-Phase Nanoglass-Ceramics Self-Calibrated Optical Thermometer.

A strategy to achieve high sensitivity of noncontact optical thermometer via the structure design of nanoglass-ceramic and the usage of Ln(3+) (Ln = Eu, Tb, Dy) luminescence as reference signal and Cr(3+) emission as temperature signal was provided. Specifically, the synthesized dual-phase glass-ceramics were evidenced to enable spatially confined doping of Ln(3+) in the hexagonal GdF3 nanocrystals and Cr(3+) in the cubic Ga2O3 nanoparticles, being beneficial to suppressing detrimental energy transfer between Ln(3+) and Cr(3+) and thus significantly enhancing their luminescence. As a consequence, completely different temperature-sensitive luminescence of Ln(3+)4f → 4f transition and Cr(3+) 3d → 3d transition in the present glass-ceramic resulted in obvious variation of Cr(3+)/Ln(3+) fluorescence intensity ratio with temperature and strikingly high detecting temperature sensitivity of 15-22% per K. We believe that this preliminary study will provide an important advance in exploring other innovative optical thermometry.

Optical spectroscopy of Cr³âº-doped transparent nano-glass ceramics for lifetime-based temperature sensing.

Transparent bulk glass ceramic containing Cr3+:LiGa5O8 nanoparticles was fabricated as an alternative for monocrystal to explore the possible application in fluorescence lifetime-based temperature sensing. Such glass ceramic exhibited deep-red luminescence upon the excitation of the wide wavelength range of visible light. Impressively, the Cr3+ lifetime dramatically decreased from 2.45 to 0.22 ms with the temperature increasing from 293 to 563 K, owing to the competition of radiation transitions from the thermally coupled 2E and 4T2 excited states. A two-level kinetic model was adopted to interpret this temperature-dependent luminescence of Cr3+, which gave a highest temperature sensitivity of 1.15% K(-1).

Tunable upconversion luminescence in self-crystallized Er(3+):K(Y(1-x)Yb(x))3F10 nano-glass-ceramics.

K(Y1-xYbx)3F10 (x = 0-1) solid-solution nanocrystals embedded glass ceramics were fabricated via glass self-crystallization. Using Eu(3+) as a structural probe, the partition of lanthanide activators into the K(Y1-xYbx)3F10 lattice was evidenced. As a consequence, color-tunable upconversion luminescence from green to red was easily realized by modifying Yb(3+) content in the Er(3+)-doped nano-glass-ceramics.

Antiviral effects against EV71 of pimprinine and its derivatives isolated from Streptomyces sp.

BACKGROUND: The pimprinine family of compounds represent very important and promising microbial metabolites for drug discovery. However, their ability in inhibiting viral infections has not yet been tested. METHODS: The antiviral activity of the pimprinine family of compounds was evaluated by determining the cytopathic effect (CPE), cell viability or plaque-forming unit (PFU), and virus yield. The mechanism of action against EV71 was determined from the virucidal activity, and effective stage and time-of-addition assays. The effects on EV71 replication were evaluated further by determining viral RNA synthesis, protein expression and cells apoptosis using the SYBR Green assays, immunofluorescence assays and flow cytometric assays, respectively. RESULTS: Pimprinethine, WS-30581 A and WS-30581 B inhibited EV71-induced CPE, reduced progeny EV71 yields, as well as prevented EV71-induced apoptosis in human rhabdomyosarcoma (RD) cells. These compounds were found to target the early stages of the EV71 replication in cells including viral RNA replication and protein synthesis. They also showed antiviral activity against ADV-7, and were slightly active against CVB3, HSV-1 and H1N1 with a few exceptions. Pimprinine was slightly active or inactive against all the viruses tested. The mechanisms by which these compounds act against the viruses tested may be similar to that demonstrated for EV71. CONCLUSION: The data described herein demonstrate that the pimprinine family of compounds are inhibitors effective against the replication of EV71 and ADV-7, so they might be feasible therapeutic agents for the treatment of viral infections.

New cytotoxic alkylated anthraquinone analogues from a soil actinomycete Streptomyces sp. WS-13394.

Four new alkylated anthraquinone analogues (1-4) were isolated from a soil actimomycete Streptomyces sp. WS-13394. The structures of compounds 1-4 were elucidated to be 1,4,6-trihydroxy-8-alkylanthraquinones by means of spectroscopic methods, including UV, one dimensional (1D), 2D-NMR and MS spectrometry. All compounds showed activities against BGC-823 and MCF-7 with IC50 from 0.99 to 3.54 µg/mL, while 2 exhibited cytotoxicity against HepG2, A875, BGC-823 and MCF-7 with IC50 2.29, 4.90, 0.99, and 1.66 µg/mL, respectively.

Complete genome sequence of antibiotic-producing Streptomyces sp. HBERC⁃20821, isolated from Wawushan Hill, Sichuan Province, China.

The complete genome of a Streptomyces capable of producing multiple antibiotics was sequenced. Strain HBERC-20821 was isolated from a soil sample collected at Wawushan Hill, Sichuan Province, China. Genomic information will facilitate our systematic genetic manipulation of the strain at the gene level, enhancing its antibiotic production.

Optimization of fungal secondary metabolites production via response surface methodology coupled with multi-parameter optimized artificial neural network model.

Filamentous fungi's secondary metabolites (SMs) possess significant application owing to their distinct structure and diverse bioactivities, yet their restricted yield levels often hinder further research and application. The study developed a response surface methodology-artificial neural network (RSM-ANN) strategy with multi-parameter optimizations of the ANN model to optimize medium for the production of two high-value fungal SMs, echinocandin E and paraherquamide A. Multi-parameter optimization of the ANN model was achieved through stratifying experimental data, fully adjusting neural network internals, and evaluating metaheuristic algorithms for optimal initial weights and biases. Experimental validation of models revealed that ANN-genetic algorithm models outperformed traditional RSM models in terms of determination coefficients, accuracy, and mean squared errors. ANN models showed outstanding robustness across a variety of fungal species, mediums, and experimental designs (Central Composite Design or Box-Behnken Design). This work refines the RSM-ANN optimization technique to increase fungal SM production efficiency, enabling industrial-scale production and applications.

Diarylamine-Guided Carboxamide Derivatives: Synthesis, Biological Evaluation, and Potential Mechanism of Action.

Diarylamines are a class of important skeleton widely existing in drugs or natural products. To discover novel diarylamine analogues as potential drugs, two series of diamide and carboxamide derivatives containing diarylamine scaffold were designed, synthesized and evaluated for their potential cytotoxic activities. The bioassay results indicated that some of the obtained compounds (C5, C6, C7, C11) exhibited good cytotoxic effect on cancer cell lines (SGC-7901, A875, HepG2), especially, compound C11 present significantly selective proliferation inhibition activity on cancer and normal cell lines (MARC145). In addition, the possible apoptosis induction for highly potential molecules was investigated, which present compound C11 could be used as novel lead compound for discovery of promising anticancer agents.

Marine Alkaloid Pityriacitrin and Its Analogues: Discovery, Structures, Synthetic Methods and Biological Properties.

Pityriacitrin is a natural marine alkaloid with a typical ß-carboline scaffold, and which has been demonstrated to exhibit diverse biological functions. The special structural features for pityriacitrin lead to the increasing research interest and the emergence of versatile derivatives, and many pityriacitrin analogues have been isolated or synthesized over the past decades. The structural diversity and evolved biological activity of these natural alkaloids can offer opportunities for the development of highly potential novel drugs with a new mechanism of action, and therefore, the aim of this brief review is to describe the discovery, synthesis, and biological properties of natural pityriacitrin and its derivatives, as well as the isolation source.

Two new dipimprinine alkaloids from soil-derived Streptomyces sp. 44414B.

Two new dipimprinine alkaloids dipimprinine E (1) and dipimprinine F (2) were isolated from Streptomyces sp. 44414B. The structure was elucidated by extensive spectroscopic analysis, including ESI-MS, HR-MS, and 1D and 2D NMR experiments. Dipimprinines F (2) showed cytotoxic activities against three tumor cell lines, including A-875, Hep G2, and H-460, with IC50 values of 26.4, 0.5, and 9.0 µg ml-1, respectively.

Herbicidal Secondary Metabolites from Actinomycetes: Structure Diversity, Modes of Action, and Their Roles in the Development of Herbicides.

Weeds had caused significant loss for crop production in the process of agriculture. Herbicides have played an important role in securing crop production. However, the high reliance on herbicides has led to environmental issues as well as the evolution of herbicide resistance. Thus, there is an urgent need for new herbicides with safer toxicological profiles and novel modes of action. Actinomycetes produce very diverse bioactive compounds, of which some show potent biopesticidal activity. The herbicidal secondary metabolites from actinomycetes can be classified into several groups, such as amino acids, peptides, nucleosides, macrolides, lactones, amide, amines, etc., some of which have been successfully developed as commercial herbicides. The structure diversity and evolved biological activity of secondary metabolites from actinomycetes can offer opportunities for the development of both directly used bioherbicides and synthetic herbicides with new target sites, and thus, this review focuses on the structure, herbicidal activity, and modes of action of secondary metabolites from actinomycetes.

Phase Selection and Structure of Low-Defect-Density γ-Al2O3 Created by Epitaxial Crystallization of Amorphous Al2O3.

A multistep phase sequence following the crystallization of amorphous Al2O3 via solid-phase epitaxy (SPE) points to methods to create low-defect-density thin films of the metastable cubic γ-Al2O3 polymorph. An amorphous Al2O3 thin film on a (0001) α-Al2O3 sapphire substrate initially transforms upon heating to form epitaxial γ-Al2O3, followed by a transformation to monoclinic θ-Al2O3, and eventually to α-Al2O3. Epitaxial γ-Al2O3 layers with low mosaic widths in X-ray rocking curves can be formed via SPE by crystallizing the γ-Al2O3 phase from amorphous Al2O3 and avoiding the microstructural inhomogeneity arising from the spatially inhomogeneous transformation to θ-Al2O3. A complementary molecular dynamics (MD) simulation indicates that the amorphous layer and γ-Al2O3 have similar Al coordination geometry, suggesting that γ-Al2O3 forms in part because it involves the minimum rearrangement of the initially amorphous configuration. The lattice parameters of γ-Al2O3 are consistent with a structure in which the majority of the Al vacancies in the spinel structure occupy sites with tetrahedral coordination, consistent with the MD results. The formation of Al vacancies at tetrahedral spinel sites in epitaxial γ-Al2O3 can minimize the epitaxial elastic deformation of γ-Al2O3 during crystallization.

Four new anthraquinones from a soil actinomycete Streptomyces sp. WS-13394 and their bioactivities.

Further chemical study of secondary metabolites from the soil actinomycete Streptomyces sp. WS-13394 resulted in the isolation of four new alkylated anthraquinone analogues (5-8). Their structures were elucidated on the basis of extensive spectroscopic analysis, including HR-ESI-MS, 1D and 2D NMR. The new compounds, together with analogues obtained before (1-4), were tested for their in vitro cytotoxicity against Huh-7 and SGC-7901.