Computational design of Tryprostatin-A derivatives as novel αß-tubulin inhibitors.

In the first part of this work, binding energies, inhibition constants and binding modes for a group of previously synthesized Tryprostatin-A (TPS-A) derivatives at the binding site of αß-tubulin have been comprehensively investigated by molecular docking study. The results represent relatively suitable binding energies for these inhibitors in the αß-tubulin binding site. In the second part, docking tools were utilized in order to design a group of novel analogues of TPS-A. The results of molecular docking reveal that these newly designed molecules have relatively lower binding energies in the pocket of αß-tubulin. Compound 26 resulted as the best docked molecule with the highest binding affinity (binding energy of -10.74 kcal/mol and calculated inhibition constant of 13.44 nM). In the last part of this study, three representative complexes were subjected to a 25 ns molecular dynamics simulation to further validate the proposed binding modes and interactions. Analysis of the simulation trajectories showed that the root mean square deviation (RMSD) profile of compound 26 was fairly stable during the whole simulation time, indicating that the orientation generated from the docking study is fairly well preserved during the entire length of the simulation. Moreover, the RMSD profiles of compounds 4 and 31 were probably stable in relation to αß-tubulin after 7 and 14 ns, and these molecular systems were well behaved thereafter. The results of the current study shed some light on the binding mode of TPS-A analogues for further experimental studies.

Protecting impact of Jaft against carbendazim induced biochemical changes in male Wistar rats.

Introduction: Pesticides are a critical tool for crop protection and control of different pests and insects. The present research conducted to evaluate the protective role of Jaft extract against oxidative pressure, biochemical variations because of limited time giveaway to carbendazim in Wistar mice males. Fresh fruits of quercus brantii were dried and the internal layer (Jaft) was collected for a hydroalcoholic extract by a maceration method at normal ambient condition. For the experimental study, twenty-four adult male rats (Wistar albino rats weighing 150-200 g) were randomized into 3 teams out of eight. Team I subserved like a vehicle treated group, received corn oil additionally to their food, while the animals in the second team got 0.1 ml carbendazim (50mg/ kg in corn oil) via oral path for nine days. Rats in group III received Jaft (500 mg/ kg orally + in carbendazim for 9 days. Blood samples were obtained by heart puncture to determine alkaline phosphatase (ALP), blood urea nitrogen (BUN), creatinine, alanine (ALT) and aspartate aminotransferases (AST); by using auto-analyzer in serum.Kidneys and liver separated from rats and provided for series of biochemical parameters homogenization like GSH and MDA stages. Result: The serum content of AST, ALT, ALP, BUN and creatinine were significantly elevated by in carbendazim treatment (group II) compared to the negative group (p<0.01).The liver enzymes operations, creatinine and BUN were significantly reduced in rats (p<0.05) when Jaft was received in a short period of time (group III). Hepatic and GSH and renal MDA stages in group (II) were clearly (p<0.05) enhanced and decreased consequently. The GSH and MDA stages content were significantly normalized in mice (p<0.05) when Jaft was received by group III. Conclusions: According to the present data, Jaft can neutralize carbendazim contain pressure of oxidative and recover the abnormal pathological injuries in Wistar mice males.

The largest subunit of human RNA polymerase III is closely related to the largest subunit of yeast and trypanosome RNA polymerase III.

In both yeast and mammalian systems, considerable progress has been made toward the characterization of the transcription factors required for transcription by RNA polymerase III. However, whereas in yeast all of the RNA polymerase III subunits have been cloned, relatively little is known about the enzyme itself in higher eukaryotes. For example, no higher eukaryotic sequence corresponding to the largest RNA polymerase III subunit is available. Here we describe the isolation of cDNAs that encode the largest subunit of human RNA polymerase III, as suggested by the observations that (1) antibodies directed against the cloned protein immunoprecipitate an active enzyme whose sensitivity to different concentrations of alpha-amanitin is that expected for human RNA polymerase III; and (2) depletion of transcription extracts with the same antibodies results in inhibition of transcription from an RNA polymerase III, but not from an RNA polymerase II, promoter. Sequence comparisons reveal that regions conserved in the RNA polymerase I, II, and III largest subunits characterized so far are also conserved in the human RNA polymerase III sequence, and thus probably perform similar functions for the human RNA polymerase III enzyme.

ECG intervals in acute bipolar and schizophrenic relapse.

Psychosis in general and acute relapse of bipolar illness, in particular, are associated with elevated catecholamine excretion, cardiovascular changes, and changes in intracellular calcium concentration. In an effort to determine if these changes result in observable ECG abnormalities, we retrospectively examined ECG parameters of acutely disturbed bipolar and schizophrenic patients. There were no discrete patterns of abnormalities, and no significant differences were observed between the two patient groups. Most ECG changes in acutely hospitalized bipolar and schizophrenic patients appear to be benign.