Binding mode of conformations and structure-based pharmacophore development for farnesyltransferase inhibitors

Farnesyltransferase (FTase) is one of the prenyltransferase family enzymes that catalyse the transfer of 15-membered isoprenoid (farnesyl) moiety to the cysteine of CAAX motif-containing proteins including Rho and Ras family of G proteins. Inhibitors of FTase act as drugs for cancer, malaria, progeria and other diseases. In the present investigation, we have developed two structure-based pharmacophore models from protein–ligand complex (3E33 and 3E37) obtained from the protein data bank. Molecular dynamics (MD) simulations were performed on the complexes, and different conformers of the same complex were generated. These conformers were undergone protein–ligand interaction fingerprint (PLIF) analysis, and the fingerprint bits have been used for structure-based pharmacophore model development. The PLIF results showed that Lys164, Tyr166, TrpB106 and TyrB361 are the major interacting residues in both the complexes. The RMSD and RMSF analyses on the MD-simulated systems showed that the absence of FPP in the complex 3E37 has significant effect in the conformational changes of the ligands. During this conformational change, some interactions between the protein and the ligands are lost, but regained after some simulations (after 2 ns). The structure-based pharmacophore models showed that the hydrophobic and acceptor contours are predominantly present in the models. The pharmacophore models were validated using reference compounds, which significantly identified as HITs with smaller RMSD values. The developed structure-based pharmacophore models are significant, and the methodology used in this study is novel from the existing methods (the original X-ray crystallographic coordination of the ligands is used for the model building). In our study, along with the original coordination of the ligand, different conformers of the same complex (protein–ligand) are used. It concluded that the developed methodology is significant for the virtual screening of novel molecules on different targets.     

1-乙基-6-氟-1,4-二氢-4-氧代-7-(4-芳酰硫代氨甲酰基-1-哌嗪基)-3-喹啉羧酸的合成及抗菌作用

Thirteen new 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(4-aroyl-thiocarbamoyl- 1 piperazinyl)-3-quinoline carboxylic acids were prepared, Their structures were characterized by elemental analysis, IR, HNMR and MS spectra.Preliminary pharmacological tests indicated that some of compounds Ia～m possess strong inhibiting activity against Escherichia coli, Bacillus subtilis and Proteus at concentration of 100 μg/ml.     

Exophytic gliomas of the spinal cord

Intradural extramedullary glial tumours of the spinal cord are rare. We report for such tumours arising from the dorsal cord. Myelography and operative findings were almost similar to that of an intradural neurofibroma. Surgical removal had resulted in rewarding neurological recovery. One of them had a recurrence after six years and was re-explored. Anterolateral attachment near the root entry zone suggests its origin probably from the spinal cord with an exophytic growth.     

1.5 tesla magnetic resonance imaging of acute spinal trauma

Fifty patients with spinal injury above L2 were studied with MRI; forty-two had initial and followup studies permitting correlation of MRI abnormalities with neurologic improvement. Two discrete patterns of MRI abnormality were identified, presumably representing cord hemorrhage and edema respectively. A third pattern appeared to represent a mixed type of injury. The correlation between the MRI patterns of cord injury and neurologic recovery was excellent. The ability of MRI to demonstrate and characterize acute cord injury appears to exceed that of other diagnostic techniques.     

Aid for impacted foreign body ear

Foreign body ear is a common problem. When it is impacted it can tax the resorces of each of us. An attempt is made in this paper to make a customable foreign body removal hook using a lumbar puncture needle.     

大狼毒三萜类化学成分的研究

自大戟科(Euphorbiaceae)植物大狼毒(Euphorbia nematocypha Hand—Mazz)根的乙醇提取物的苯溶解部分,经20%AgNO₃硅胶层析,分离得到七个三萜类成分。根据光谱(IR,EIMS,¹H—NMR和¹³C—NMR)和化学方法,确定其中一个化合物为新化合物,命名为大狼毒醇(nematocyphol,Ⅳa),其它化合物为已知物:印度荆芥醇乙酸酯(nepehinol acetate Ⅰ),日尔曼醇乙酸酯(germanicol acetate Ⅱ),大戟醇(euphol,Ⅲ),蒲公英醇(taraxasterol,Ⅴa),24-亚甲基环阿尔廷醇(24-methylenecycloartanol,Ⅴa)和印度荆芥醇(nepehinol,Ⅶa)。这些化合物均为首次从大狼毒中得到。     

亮氨酸脑啡肽的电子结构及构效关系研究

对亮氨酸脑啡肽进行了量子化学(INDO)计算,研究其电子结构特征,讨论其活性部位、作用机理及构效关系。同吗啡和R31833进行了活性部位的电子结构与空间结构比较,推断它们的活性药效结构具有共同特点,与阿片受体相互作用时作用方式相同,作用部位有对应关系,因而具有相同的药理性质。