ABSTRACT
Caerulomycin A (CRM A) is the first example of natural caerulomycins with a 2,2'-bipyridyl ring core and 6-aldoxime functional group from Streptomyces caeruleus and recently from marine-derived Actinoalloteichus cyanogriseus WH1-2216-6. Our previous study revealed that CRM A showed anti-tumor activity against human colorectal cancer (CRC) both in vitro and in vivo. Because some intestinal flora can affect the occurrence and development of CRC, the influence of CRM A on the intestinal flora is worthy of study in Sprague-Dawley (SD) rats. The high throughput sequencing of the V3-V4 hypervariable region in bacterial 16S rDNA gene results showed that the CRM A affected the diversity of intestinal flora of the SD rats treated with CRM A for 2, 3 and 4 weeks. Further analysis indicated that the abundance of genera Prevotella_1, Prevotellaceae_UCG-001, and Lactobacillus were increased while the that of genera Alloprevotella and Ruminiclostridium_1 were decreased. For the CRC related intestinal flora, the abundance of genera Bacteroides, Fusobacterium, Enterococcus, Escherichia-Shigella, Klebsiella, Streptococcus, Ruminococcus_2, and Peptococcus of SD rats treated with CRM A were decreased, while that of abundance of genera Bifidobacterium, Lactobacillus, Faecalibacterium, Blautia, Oscillibacter, and Clostridium were increased. The results indicated that CRM A could influence the intestinal flora by inhibiting some species of harmful flora and improving the beneficial bacteria in intestinal flora in the SD rats. The results may provide a new idea for revealing the mechanism of the anti-CRC activity of CRM A.
Subject(s)
Gastrointestinal Microbiome/drug effects , Pyridines/pharmacology , Animals , Antineoplastic Agents/pharmacology , Cell Line, Tumor/drug effects , Colorectal Neoplasms/genetics , Disease Models, Animal , Rats , Rats, Sprague-DawleyABSTRACT
A chemical-epigenetic method was used to enhance the chemodiversity of a marine algicolous fungus. Apart from thirteen known compounds, (+)-brevianamide R ((+)-3), (â)-brevianamide R ((â)-3), (+)-brevianamide Q ((+)-4), (â)-brevianamide Q ((â)-4), brevianamide V ((+)-5), brevianamide W ((â)-5), brevianamide K (6), diorcinol B (7), diorcinol C (8), diorcinol E (9), diorcinol J (10), diorcinol (11), 4-methoxycarbonyldiorcinol (12), two new compounds, (+)- and (â)-brevianamide X ((+)- and (â)- 2)), as well as a new naturally occurring one, 3-[6-(2-methylpropyl)-2-oxo-1H-pyrazin-3-yl]propanamide (1), were isolated from chemical-epigenetic cultures of Aspergillus versicolor OUCMDZ-2738 with 10 µM vorinostat (SAHA). Compared to cultures in the same medium without SAHA, compounds 1â»4, 8, 9, 11, and 12 were solely observed under SAHA condition. The structures of these compounds were elucidated based on spectroscopic analysis, specific rotation analysis, ECD, and X-ray crystallographic analysis. (±)-3, (±)-4, and (±)-5 were further resolved into the corresponding optically pure enantiomers and their absolute configurations were determined for the first time. Compounds 11 and 12 showed selective antibacterial against Pseudomonas aeruginosa with a minimum inhibitory concentration (MIC) of 17.4 and 13.9 µM, respectively. Compound 10 exhibited better α-glucosidase inhibitory activity than the assay control acarbose with IC50 values of 117.3 and 255.3 µM, respectively.
Subject(s)
Anti-Bacterial Agents/pharmacology , Aspergillus/chemistry , Biological Products/pharmacology , Glycoside Hydrolase Inhibitors/pharmacology , Ulva/microbiology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/metabolism , Aspergillus/drug effects , Aspergillus/genetics , Aspergillus/metabolism , Biological Products/chemistry , Biological Products/isolation & purification , Biological Products/metabolism , Biosynthetic Pathways/genetics , Chemical Engineering/methods , Crystallography, X-Ray , Diketopiperazines/chemistry , Diketopiperazines/isolation & purification , Diketopiperazines/metabolism , Diketopiperazines/pharmacology , Enzyme Assays , Epigenesis, Genetic/drug effects , Fermentation , Glycoside Hydrolase Inhibitors/isolation & purification , Inhibitory Concentration 50 , Methylation/drug effects , Microbial Sensitivity Tests , Molecular Structure , Phenyl Ethers/chemistry , Phenyl Ethers/isolation & purification , Phenyl Ethers/metabolism , Phenyl Ethers/pharmacology , Pseudomonas aeruginosa/drug effects , Stereoisomerism , Vorinostat/pharmacology , alpha-Glucosidases/metabolismABSTRACT
This review covers the literature published by chemists from China during the 2015-2016 on natural products (NPs), with 1,985 citations referring to 6,944 new compounds isolated from marine or terrestrial microorganisms, plants, and animals. The emphasis is on 730 new compounds with a novel skeleton or/and significant bioactivity, together with their source organism and country of origin.
