ABSTRACT
OBJECTIVE:To study 3D-QSAR of pyridine heterocyclic ring PI3K inhibitor as anti-renal cancer drug,and to provide reference for the design and R&D of new anti-renal cancer inhibitors. METHODS:The data of structure and active value (pIC50) of 30 pyridine heterocyclic ring PI3K inhibitors were collected. After Sybyl-X 1.1 software used for molecular superimposition, CoMFA and CoMSIA model were established to investigate three dimensional field, electrostatic field, hydrophobic field,hydrogen bond donor site and hydrogen bond acceptor field of PI3K inhibitor molecule. Sybyl-X 1.1 software was used for molecular docking,and the mechanism of PI3K inhibitor molecule and receptor target protein were analyzed. PyMOL V1.5 software was used to design new PI3K inhibitor molecules. The activity of inhibitor molecules was predicted with CoMFA and CoMSIA model. RESULTS:The cross validation coefficients of CoMFA and CoMSIA model were 0.617 and 0.601, fitting validation coefficients were 0.969 and 0.974,and external predictive correlation coefficients were 0.656 and 0.670, respectively. In CoMFA model, contributions of three dimensional field and electrostatic field were 56.2% and 43.8%respectively. In CoMSIA model,contributions of three dimensional field,electrostatic field,hydrophobic field,hydrogen bond donor site and hydrogen bond acceptor field were 41.0%,31.3%,21.1%,2.4%,4.2%. After molecular superimposition,small steric hindrance,strong positive and hydrophilic groups introduced nearby R1 group of common skeleton could help to enhance the activity of molecules. The results of molecular docking showed that PI3K inhibitor molecule formed three hydrogen bonds with the key amino acids ALA805,VAL882 and THR887 of receptor target protein,with the length of 1.84,1.99,1.99 ?. According to above information,6 new molecules were designed,among which predicted pIC50 of 2 molecules with higher activity were 3.211,3.247(CoMFA method)and 3.238,3.222(CoMSIA method). CONCLUSIONS:Established new CoMFA and CoMSIA model have good prediction ability and statistical stability. Contribution of three dimensional field is higher than that of electrostatic field,and the influence of hydrophobic field on molecular activity can not be ignored. Pyridine heterocyclic ring PI3K inhibitors have strong hydrogen bonding role with receptor target protein. 3D-QSAR can provide reference for the design,reconstruction and drug R&D of new PI3K inhibitor molecule.
ABSTRACT
A microwave digestion system was preparation for the digestion of the sediment samples of 16 stations in the Southe mid_Atlantic ridge by using HNO3_H2 O2_HF as the digestion reagent. The rare earth elements ( RE ) in sediments were determined by inductively coupled plasma mass spectrometry, and distribution characteristics of rare earth elements were studied. The microwave digestion_ICP_MS method was used for the determination of rare earth elements with a good linear relationship ( r=0 . 9997-1 . 0000 ) for each element. The detection limit reached ng/L level, the relative standard deviation ( RSD, n=3 ) was less than 3% and the relative error was 6%. The total amount of rare earth elements (ΣRE) in sediment samples from 16 stations varied in the range of 37. 25-134. 77 μg/g, the ratio range of light RE/heavy RE ( LRE/HRE) was 0 . 61-1 . 70 , the average value was 1 . 27 , and the enrichment of light rare earth elements in sediments was slightly obvious. The RE distribution patterns were basically the same in each station with obvious fractionation between LRE and HRE. The RE distribution patterns were also similar in sediments from different sources with slightly difference between terrestrial and marine sediments. The δEu and δCe in the sediments had negative anomaly which showed that the rare earth elements in sediments came from the seawater. This study first analyzed the content and distribution of rare earth elements in the southern Atlantic, providing data and technical support for further study of the distribution of rare earth elements in the Atlantic.
ABSTRACT
Objective:To explore the therapeutic effect of the extraction of bone-melon injection for the earlier fracture.Method:100 patients with early fracture were divided into two groups.50 cases in the treatment group used the extraction of the bone-melon injection and 50 cases in the controlled group used compound ossotide injections.Their curative effects were judged according to their healing time,level of relieving pain and functional recovery condition.Result: The patients in the treatment group healed earlier(P