Due to increased drug and radiation tolerance, there is an urgent need to develop novel anticancer agents.In our previous study, we performed a series of structural modifications of ursolic acid (UA), a natural product of pentacyclic triterpenes, and found UA232, a derivative with stronger anti-tumor activity.In vitro experiments showed that UA232 inhibited proliferation, induced G0/G1 arrest, and promoted apoptosis in human breast cancer and cervical cancer cells.Mechanistic studies revealed that UA232 promoted apoptosis and induced protective autophagy via the protein kinase R-like endoplasmic reticulum kinase/activating transcription factor 4/C/EBP homologous protein-mediated endoplasmic reticulum stress.In addition, we also found that UA232 induced lysosomal biogenesis, increased lysosomal membrane permeability, promoted lysosomal protease release, and led to lysosome-dependent cell death.Furthermore, UA232 suppressed tumor growth in a mouse xenograft model.In conclusion, our study revealed that UA232 exerts multiple pharmacological effects against breast and cervical cancers by simultaneously triggering endoplasmic reticulum stress and lysosomal dysfunction.Thus, UA232 may be a promising drug candidate for cancer treatment.
Three novel 24,30-dinortriterpenoids named paeonenoides A–C (1–3) and the four related acetonide derivatives 4–7, most likely artifacts of isolation, together with a known triterpenoid, akebonic acid (8), were isolated from the root cortex of Paeonia veitchii. Their structures were established by spectroscopic means. The 24,30-dinor skeleton of triterpenoids occurs rarely in nature.
Synsepalum dulcifificum is an evergreen shrub native of tropical West Africa. It is very effective against a variety of diseases. However, the phytochemical investigation on this plant is limited till now. In our current study, seventeen compounds were isolated and identified from the ethyl acetate extract of the leaves. All of the compounds were obtained from S. dulcifificum for the first time. Compounds 4 and 9 were isolated from natural source for the second time. Moreover, the antioxidant activities of compounds 1, 4, 5, 9-11, and 15 were evaluated firstly. Compounds 6, 7, 13, and 14 exhibited significant antioxidant activity in DPPH and ABTS + assays, suggesting their potential application for an antioxidant drug.
Actinobacteria are a phylum of bacteria known for their potential in producing structurally diversified natural products that are always associated with a broad range of biological activities. In this paper, using an H5N1 pseudo-typed virus drug screening system combined with a bioassay guided purification approach, an antiviral butanolide (1) was identified from the culture broth of Streptomyces sp. SMU03, a bacterium isolated from the feces of Elephas maximus in Yunnan province, China. This compound displayed broad and potent activity against a panel of influenza viruses including H1N1 and H3N2 subtypes, as well as influenza B virus and clinical isolates with half maximal inhibitory concentration values (IC50) in the range of 0.29 to 12 µg/mL. In addition, 1 was also active against oseltamivir-resistant influenza virus strain of A/PR/8/34 with NA-H274Y mutation. Studies on the detailed modes of action suggested that 1 functioned by interfering with the fusogenic process of hemagglutinin (HA) of influenza A virus (IAV), thereby blocking the entry of virus into host cells. Furthermore, the anti-IAV activity of 1 was assessed with infected BALB/c mice, of which the appearance, weight, and histopathological changes in the infected lungs were significantly alleviated compared with the no-drug-treated group. Conclusively, these results provide evidence that natural products derived from microbes residing in animal intestines might be a good source for antiviral drug discovery.
We report an urease negative Cryptococcus neoformans derived from pigeon dropping. This isolate produced brown pigmented colonies on cornmeal Tween-80 agar with 300 micrograms/ml caffeic acid, but was failure to hydrolyze urea. More identification tests were performed for this isolate, such as assimilation and fermentation of carbohydrates, nitrate assimilation, production of starch like compound, growth on GCP medium, germ tube formation and inoculation of mice, ect. Most of the results showed that the microbiological characteristics of the isolate were typical of C. neoformans except for negative urease test. Even though there has been a report about an urease negative C. neoformans derived from an AIDS patient, but we have never found any report about isolation from pigeon dropping or nature environment. We should pay attention to the exist of this atypical strain of C. neoformans in nature environment and the possibility of infection to human being. Additionally, we also be aware of the possibility of neglect when this urease negative C. neoformans is identified with urease test.
Actinomycetes are regarded as important sources for the generation of various bioactive secondary metabolites with rich chemical and bioactive diversities. Amycolatopsis falls under the rare actinomycete genus with the potential to produce antibiotics. In this review, all literatures were searched in the Web of Science, Google Scholar and PubMed up to March 2021. The keywords used in the search strategy were "Amycolatopsis", "secondary metabolite", "new or novel compound", "bioactivity", "biosynthetic pathway" and "derivatives". The objective in this review is to summarize the chemical structures and biological activities of secondary metabolites from the genus Amycolatopsis. A total of 159 compounds derived from 8 known and 18 unidentified species are summarized in this paper. These secondary metabolites are mainly categorized into polyphenols, linear polyketides, macrolides, macrolactams, thiazolyl peptides, cyclic peptides, glycopeptides, amide and amino derivatives, glycoside derivatives, enediyne derivatives and sesquiterpenes. Meanwhile, they mainly showed unique antimicrobial, anti-cancer, antioxidant, anti-hyperglycemic, and enzyme inhibition activities. In addition, the biosynthetic pathways of several potent bioactive compounds and derivatives are included and the prospect of the chemical substances obtained from Amycolatopsis is also discussed to provide ideas for their implementation in the field of therapeutics and drug discovery.
Six compounds were isolated from the culture broth of the alkalophilic actinomycete YIM-80147.Their structures were identified respectively as:P371A2 (1),4-hydroxymethyl-3-(1-hydroxy-6-methyl-heptyl)-dihydro-furan-2-one (2),nonactic acid (3),homononactinic acid (4),p-hydroxycinnamic acid (5),ferulic acid (6) on the basis of the spectroscopic analysis.
Abstract magnified image Two new solanapyrone analogues, solanapyrones N and O ( 1 and 2 , resp.), and three known compounds, solanapyrone C ( 3 ), nigrosporalactone ( 4 ), and phomalactone ( 5 ), were isolated from the fermentation culture of Nigrospora sp. YB‐141, an endophytic fungus isolated from Azadirachta indica A. Juss . The structures of the new compounds were elucidated on the basis of spectroscopic analysis. The antifungal activities of 1 – 5 towards seven phytopathogenic fungi were tested. Most of the compounds exhibited no or only weak antifungal activities.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)