Search

A series of styrylquinolines was designed and synthesized based on the four main quinoline scaffolds including oxine, chloroxine and quinolines substituted with a hydroxyl group or chlorine atom at the C4 position. All of the compounds were tested for their anticancer activity on wild-type colon cancer cells (HCT 116) and those with a p53 deletion. Analysis of SAR revealed the importance of electron-withdrawing substituents in the styryl part and chelating properties in the quinoline ring. The compounds that were more active were also tested on a panel of four cancer cell lines with mutations in TP53 tumor suppressor gene. The results suggest that styrylquinolines induce cell cycle arrest and activate a p53-independent apoptosis. The apparent mechanism of action was studied for the most promising compounds, which produced reactive oxygen species and changed the cellular redox balance., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Thiosemicarbazones (TSC) are a subclass of iron-chelating agents that are believed to have an anticancer activity. The high potential for the application of this compound class can be illustrated by a fact that three TSC have entered clinical trials. The ability to chelate metal ions results in several biochemical changes in the cellular metabolism and growth. An important factor that determines the antitumor activity of TSC is a level of iron regulatory proteins and the antioxidant potential that is specific for each type of cancer cell. However, despite the increasing interest in TSC, their mechanism of anticancer activity is still unclear. For a more effective and rational design, it is crucial to determine and describe the abovementioned issues. In this report, we describe a series of new TSC that are designed on the four main structural scaffolds. The anticancer activity of these compounds was evaluated against a panel of cancer cell lines including colon and breast cancers and gliomas. Special attention was paid to the metal-dependent proteins. The impact of the tested TSC on the cell cycle and redox homeostasis was also determined. These results confirm a p53-independent mechanism of apoptosis., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Quinazoline derivatives constitute a large family of small-molecule inhibitors of tyrosine kinases. In the current study, the p53 protein reactivator CP-31398 was tested against a panel of kinases on the assumption that it was structurally similar to other active inhibitors. Although it was found to be active in the enzyme-based assay, this compound did not block the proliferation of cancer cells at a feasible concentration level. The styrylquinazoline was used to design new structures that might be potential multitarget inhibitors. Subsequently, a series of compounds was obtained and characterized. Their inhibitory activity in a panel of tyrosine kinases had an antiproliferative effect against several cancer cell lines that have different expression levels of those proteins. The mode of protein interaction was tested for the most active compound in docking experiments., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Glycoconjugates are combinations of sugar moieties with organic compounds. Due to their biological resemblance, such structures often have properties that are desirable for drugs. In this study we designed and synthesised several glycoconjugates from small molecular quinolines and substituted gluco- and galactopyranosyl amines. Although the parent quinoline compounds were inactive in affordable concentrations, the glycoconjugates that were obtained appeared to be cytotoxic against cancer cells at the micromolar level. When combined with copper ions, their activity increased even further. Their mechanism of action is connected to the formation of reactive oxygen species and the intercalation of DNA., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)