Isolated sodium deoxycholate was almost as effective as the phosphatidylcholine formulation, at clinical concentrations, in reducing the viability of mature adipocytes over time. Similar cytotoxic effects of phosphatidylcholine formulation on normal foreskin fibroblasts, endothelial cells, and human skeletal muscle cells also were observed. The data prove that the formulation acts in a nonspecific manner and that its unintentional administration to other tissues causes cell death.
Abstract-Hybrid back propagation based genetic algorithm approach is a popular way to train neural networks for weather prediction. The major drawback of this method is that weather parameters were assumed to be independent of each other and their temporal relation with one another was not considered. So in the present research a modified time series based weather prediction model is proposed to eliminate the problems incurred in hybrid BP/GA technique. The results are very encouraging; the proposed temporal weather prediction model outperforms the previous models while performing for dynamic and chaotic weather conditions.
In this report, novel unsymmetrical azines have been designed and synthesised by using one pot approach. Further, they were evaluated as quorum sensing inhibitors.
Introduction:Quorum sensing inhibition (QSI) is one of the vital tools to overcome emerging virulence of pathogenic bacteria which aims at curbing bacterial resistance. Targeting QS (quorum sensing) as chemotherapy is less likely to generate resistance among pathogens as it targets only the adaptation and not the survival mechanism of the pathogen. Several QS inhibitors were developed in the recent past but none of them managed to have clinical application due to known toxic effects for human consumption. A rapid development of QS inhibitor drugs could be achieved by verification of the QSI activity of drugs which are already in clinical use with known pharmacology. Recently, a known FDA approved clinical drug niclosamide belonging to an anthelmintic class is found to exhibit QSI activity.
Methods: We have focused our study on Albendazole, another FDA approved clinical drug belonging to the same class for its potential to act as QSI. The structure-based molecular docking is used for finding putative interactions made by this drug with the CviR and LasB receptor protein of Chromobacterium violaceum and Pseudomonas aeruginosa , respectively. Further, the in vitro activity of this drug has been evaluated by employing CviR and LasB receptor-based bioassay. The efficacy of this drug alone and in combination with antibiotic Tobramycin to inhibit P. aeruginosa based biofilms was also analyzed by developing the biofilms on chambered glass slides and performing anti-biofilm assay.
Results: Further, this drug found to inhibit purple pigment violacein production in C. violaceum , which is under the control of C6-AHL-CviR mediated QS in this human pathogen. The in vivo bioassays results suggested that albendazole has great potential to act as a QS inhibitor as found inhibiting violacein production in C. violaceum and biofilm formation in P. aeruginosa , respectively.
Conclusion: It is that structure-based molecular docking guided bioassay evaluation is an efficient tool for finding the new therapeutic use of old drugs which could have more chances to come easily in clinical application for their newly identified therapeutic uses.
A series of novel N,N-disubstituted biguanides (8a-8j) have been synthesized using varied secondary amines and cyanoguanidine under microwave irradiation. All the synthesized compounds were evaluated for quorum sensing inhibition (QSI) activity using Chromobacterium violaceum (ATCC12472)-based bioassay. Out of these ten compounds, two compounds 8a and 8g (IC 50 = 179 and 120 lM) showed maximum QSI activity. Decrease in violacein production was observed in the range of 0.2-200 lM concentration for these respective compounds. The molecular docking studies revealed that N,N-disubstituted biguanides shared structural complementarity with CviR domain. Furthermore, TOPKAT analysis on Ames mutagenicity and carcinogenicity models had shown that this class of compounds has least probability (0.000-0.009) of exhibiting toxicity in experimental models.
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