HN-1

Harmful algal blooms cause serious problems worldwide due to large quantities of cyanotoxins produced by cyanobacteria in eutrophic water. In this study, a new compound named 2-(3, 4-dihydroxy-2-methoxyphenyl)-1, 3-benzodioxole-5-carbaldehyde (Compound 1), together with one known compound, 3, 4-dihydroxybenzalacetone (DBL), was purified from Phellinus noxius HN-1 (CCTCC M 2016242). Compound 1 and DBL displayed activity against the cyanobacteria Microcystis aeruginosa with a half maximal effective concentration of 21 and 5 μg/mL, respectively. Scanning electron and transmission electron microscopic observations showed that the compounds caused serious damage and significant lysis to M. aeruginosa cells. qRT-PCR assay indicated that compound 1 and DBL exposure up-regulated the expression of gene mcyB and down-regulated the expression of genes ftsZ, psbA1, and glmS in M. aeruginosa. This study provides the first evidence of bactericidal activity of a new compound and DBL. In summary, our results suggest that compound 1 and DBL might be developed as naturally-based biocontrol agents.

Background: Less than 0.5% of intravenously injected drugs reach tumors, contributing to side effects. To limit damage to healthy cells, various delivery vectors have been formulated; yet, previously developed vectors suffer from poor penetration into solid tumors. This issue was resolved by the discovery of HN-1 peptide isolated via biopanning a phage-display library. HN-1 targets human head and neck squamous cell carcinoma (HNSCC) (breast, thyroid; potentially lung, cervix, uterine, colon cancer), translocates across the cell membrane, and efficiently infiltrates solid tumors. HN-1 peptide has been conjugated to various anticancer drugs and imaging agents though the identity of its receptor remained enigmatic. Aim: To decipher the clues that pointed to retinoblastoma (Rb)-regulated discoidin-domain receptor 1 as the putative receptor for HN-1 is described. Methods: HN-1 peptide was synthesized and purified using reverse-phase high-performance liquid chromatography and gel electrophoresis. The predicted mass was confirmed by mass spectroscopy.

Ultra-fast performance liquid chromatography-mass spectrometry( UFLC-MS/MS) was used to study the anti-inflammatory active ingredient of Millettia pachyloba,6-methoxy-8,8-dimethyl-3-( 2,4,5-trimethoxyphenyl)-4 H,8 H-pyrano[2,3-f]chromen-4-one( HN-1),in liver microsomes of rats,mice,rhesus monkeys,Beagle dogs and humans metabolic stability,and compare the metabolic differences between different species. The metabolic phenotype in human liver microsomes was determined by chemical inhibitor method. Using UPLC-Q-TOF-MS/MS detection method,the in vitro metabolites of various liver microsomes were preliminarily inferred by comparing the samples incubated for 0 min and 60 min in vitro. The metabolites of HN-1 in SD rats were presumed by comparing feces,urine,plasma blanks and samples after administration. The results showed that the metabolism of HN-1 in various liver microsomes was stable,and the metabolic properties of dog and human liver microsomes were the closest. It is mainly catabolized by CYP1 A1,CYP2 D6 and CYP3 A4 isoenzymes in human liver microsomes. The metabolites of HN-1 in vitro and in vivo,including 3 in vitro metabolites and5 in vivo metabolites,were preliminarily estimated. The results laid the foundation for further pharmacological studies of HN-1.