Crystal structures of biogenic amine derivative Schiff bases, and these compounds modulatory effect on cell cycle arrest and cell death in lung cancer cells
Özet
Cancer continues to be a global health problem, and this problem requires the development of targeted anticancer agents. Syntheses of different derivatives of Schiff bases have attracted serious attention in cancer research due to the potential of this group of compounds as anticancer agents. For this purpose, the biogenic amine derivative Schiff bases (Schf 1-3) were synthesised. The solid-state structure and geometry of Schf-2 and Schf-3 were determined using single crystal X-ray structural analysis for the first time in this study. The isolated compounds were characterised by NMR (1H and 13C) spectroscopy, mass analysis, and single crystal X-ray crystallography. The cytotoxic activities of these compounds against lung cancer and normal lung cells were determined by the WST-8 assay. In addition, mRNA expression levels of cell death, cell cycle, and ER stress related genes were determined by qPCR. Besides, ER stress, apoptosis, and related signaling proteins were determined by ELISA. Moreover, necrosis, early and late apoptosis, and cell cycle were determined by Flow cytometry. The most effective % viability activity is Schf-1, and IC50 value are 60.22% (27.73 mu M) (LogIC50:1.443) in A549 cells. All compounds increased in MAPK gene expressions, also, gene expressions of HSP27, HSP40, HSP60, HSP70, HSP90 and AKT decreased by these compounds in A549 cells. Moreover, GRP78, Caspase-3, p-AKT, and MAPK protein levels were upregulated by these compounds. Furthermore, cell cycle, necrosis, and apoptosis are regulated by these molecules. Our findings indicate that these compounds have potential properties that suppress HSP genes and activate ER stress related apoptotic cell death and are notable for drug-improving studies.
