Enzyme Inhibitor (Hope Medicine)

In this article, a series of calix[4]arenes derivatized with isatin derivatives at the phenolic-O position were synthesized as potential theranostic molecules for antitumor therapy. The cytotoxic mechanism of action of the synthesized compounds was determined by Alamar Blue assay and flow cytometry using MCF-7, MDA-MB-231, DLD1, HeLa and A549 human cancer cell lines and their ability to penetrate into PNT1A healthy epithelial cells. To detect DNA damage, the Comet test was applied after the synthesized compounds interacted with the cells. As a result, it was found that treated cells had abnormal tail nuclei and damaged DNA structures compared with untreated cells. Within the scope of enzyme inhibition experiments, studies were carried out on aromatase and COX-2 enzymes and it was determined that the compounds in the series showed inhibitory activity at varying rates. Especially compounds CLX-A3, CLX-A4, CLX-B3 and CLX-B5 attract attention with their enzyme inhibitor potential. Also, the antioxidant activities of the compounds whose synthesis was completed were also investigated and it was observed that the examined derivatives also had antioxidant activity potential. As a result of the antibacterial and antifungal test performed with broth microdilution, it was observed that the compounds had significant antibacterial and antifungal activity. The lowest MIC values were recorded as 0.006 mg/ml against Sarcina lutea and 0.048 against Candida albicans. In addition, the compound CLX-B3was observed to be effective against all strains including, Klebsiella pneumoniae and Salmonella enteritidis (Gram-negative pathogenic bacteria).

Carbon disulfide (CS₂) is a widely used enzyme inhibitor with cytotoxic properties, commonly employed in viscose fibers and cellophane production due to its non-polar characteristics. In industry, CS₂ is often removed by aeration, however, residual CS₂ may enter the wastewater treatment plants, impacting the performance of nitrifying sludge. Currently, there is a notable dearth of research on the response of nitrifying sludge to CS₂-induced stress. This study delves into the alterations in the performance of nitrifying sludge under short-term and long-term CS₂ stress, scrutinizes the toxic effects of CS₂ on microbial cells, elucidates the succession of microbial community structure, and delineates changes in microbial metabolic products. The findings from short-term CS₂ stress revealed that low concentrations of CS₂ induced oxidative stress damage, which was subsequently repaired in cells. However, at concentrations of 100-200 mg/L, CS₂ inhibited reactive oxygen species, superoxide dismutase, and catalase, which are associated with metabolic and antioxidant activities. The inhibition of nitrite oxidoreductase activity by high concentrations of CS₂ was attributed to its impact on the enzyme's conformation. Prolonged CS₂ stress resulted in an increase in the secretion of soluble extracellular polymeric substances in sludge, while CS₂ was assimilated into sulfate. The analysis of sludge microbial community structure revealed a decline in the relative abundance of Rhodanobacter, which is associated with nitrification, and an increase in Sinomonas, involved in sulfur oxidation. Metabolite analysis results demonstrated that high concentrations of CS₂ affect pantothenate and CoA biosynthesis, purine metabolism, and glutathione metabolism. This study elucidated the microbial response mechanism of nitrifying sludge under short-term and long-term CS₂ stress. It also clarified the composition and function of microbial ecosystems, and identified key bacterial species and metabolites. It provides a basis for future research to reduce CS₂ inhibition through approaches such as the addition of metal ions, the selection of efficient CS₂-degrading strains, and the modification of strain metabolic pathways.