MDR-involved human glutathione transferases (hGSTs) are targets for inhibition by 2,2'-dihydroxybenzophenones and N-carbonyl analogues

Over expression of human GSTA1-1 in tumour cells is part of MDR mechanisms. Substituted 2-hydroxybenzophenones are ubiquitous in naturally occurring and synthetic compounds, exhibiting important biological activities. 2,2’-Dihydroxybenzophenones and N-carbonyl analogues, structurally, are ringopened forms of xanthone analogues which we reported recently as hGSTA1-1 inhibitors. The present study combined GST inhibition screening, in silico molecular docking and enzyme inhibition kinetics, revealing four analogues with strong inhibitory potency (IC50 = 0.18-1.8 μM) and modest cytotoxic activity for Caco2 cell line (LC50 = 35 to > 400 μM), thus being useful as lead structures for the design of new inhibitors against hGSTs

Biomimetic Dyes in Biotechnology

Downstream processing refers to all the technologies that are responsible for the production of pure products after fermentation. Therefore, if one were to produce, for example, a protein, one would start with an appropriate bio-reactor containing native or engineered cells. The first step would be to separate the cells from the broth; if the product is an intra-cellular one, one would subsequently disrupt the cells to release the intra-cellular products and then embark on a clarification process to obtain a clear extract containing the protein of interest. The next step is to apply a whole series of high resolution purification techniques, particularly chromatographic steps, prior to subsequently ending up with pure protein. Therefore, downstream processing entails the execution of primary recovery stages followed by a series of high-resolution steps where we add value to the final product and then hopefully end up with pure homogeneous protein. Special interest is focused in this report on the high resolution stages of the process leading to pure product and particularly those steps involving the most refined version of chromatography, affinity chromatography (1). The technique of affinity chromatography exploits small ligands which bind specifically and reversibly to the protein of interest. The appropriate small ligand is covalently attached to a suitable solid support matrix in such a way that we can establish that as a column