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261.
Catharanthus roseus plants produce many pharmaceutically important indole alkaloids, of which the bisindole alkaloids vinblastine and vincristine
are antineoplastic medicines and the monoindole alkaloids ajmalicine and serpentine are antihypertension drugs. C. roseus cell cultures have been studied for producing these medicines or precursors catharanthine and vindoline for almost four decades
but so far without a commercially successful process due to biological and technological limitations. The research thus focused
on the one hand on engineering the bioreactor process on the other engineering the cell factory itself. This review mainly
summarizes the progress made on biochemical engineering aspects of C. roseus cell cultures in bioreactors in the past decades and metabolic engineering of indole alkaloid production in recent years.
The paper also attempts to highlight new strategies and technologies to improve alkaloid production and bioreactor performance.
Perspectives of metabolic engineering to create new cell lines for large-scale production of indole alkaloids in bioreactors
and effective combination of these up- and down-stream processing are presented. 相似文献
262.
Daniel S. Wenholz Ming Zeng Cong Ma Marcin Mielczarek Xiao Yang Mohan Bhadbhade David St. C. Black Peter J. Lewis Renate Griffith Naresh Kumar 《Bioorganic & medicinal chemistry letters》2017,27(18):4302-4308
Knoevenagel condensation was employed to generate a set of molecules potentially capable of inhibiting the RNA polymerase-σ70/σA interaction in bacteria. Synthesis was achieved via reactions between a variety of indole-7-carbaldehydes and rhodanine, N-allylrhodanine, barbituric acid or thiobarbituric acid. A library of structurally diverse compounds was examined by enzyme-linked immunosorbent assay (ELISA) to assess the inhibition of the targeted protein–protein interaction. Inhibition of bacterial growth was also evaluated using Bacillus subtilis and Escherichia coli cultures. The structure–activity relationship studies demonstrated the significance of particular structural features of the synthesized molecules for RNA polymerase-σ70/σA interaction inhibition and antibacterial activity. Docking was investigated as an in silico method for the further development of the compounds. 相似文献
263.
Quercetin is one of the naturally occurring polyphenol flavonoid predominantly known for antidiabetic activity. In the present study, by considering the structural requirements, twenty two novel chromone derivatives (5–26) as α-amylase inhibitor were designed and subsequently in silico evaluated for drug likeness behavior. Designed compounds were synthesized, characterized by spectral analysis and finally evaluated for the inhibition of α-amylase activity by in vitro assay. Tested compounds exhibited significant to weak activity with IC50 range of 12–125 µM. Among the tested compounds, analogues 5, 8, 12, 13, 15, 17 and 22 exhibited significant human α-amylase inhibitory activity with IC50 values <25 µM, which can be further explored as anti-hyperglycemic agents. Putative binding mode of the significant and least active α-amylase inhibitors with the target enzyme was also explored by the docking studies. 相似文献
264.