Synthesis, Characterization and Anticancer Efficacy Evaluation of Benzoxanthone Compounds toward Gastric Cancer SGC-7901

Abstract

Three benzoxanthone derivatives were synthesized through a new photochemical strategy. The in vitro cytotoxic activity of these compounds was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and their partition coefficients (logP) were measured by shake flask method. The pKa values of the compounds were detected by potentionmetric titration. The interaction of the compounds with calf thymus DNA (CT-DNA) was investigated by electronic absorption, luminescence spectra and viscosity. A molecular docking analysis was performed. The antitumor efficacy of the compounds was evaluated by cell apoptosis, cell cycle arrest, intracellular Ca2+ concentrations and reactive oxygen species (ROS) levels. The mitochondrial membrane potential was assayed using JC-1 (5,5′,6,6′-tetrachloro-1,1,3′,3′-tetraethyl-imidacarbocyanine iodide) as the fluorescence probe. The expression of Bcl-2 family protein, caspase 3 and poly ADP-ribose polymerase (PARP) was explored by western blot. The results showed that the compounds induced apoptosis through a ROS-mediated mitochondrial dysfunction pathway. This work provides an efficient approach to synthesize benzoxanthone derivatives, and is helpful for understanding the apoptotic mechanism.

Procjena afiniteta vezanja DNA ksantenskih spojeva

“…Spectrophotometric titration as one of them correlates with the way in which these molecules interact with DNA, whereby the insertion of small molecules into adjacent base pairs provides a number of ways in which intercalation and groove binding play a key role. 2,3 This study was undertaken to explore the molecular mechanisms of interaction of xanthene derivatives with CT-DNA.…”

Apoptosis-Related Gene-Mediated Cell Death Pattern Induces Immunosuppression and Immunotherapy Resistance in Gastric Cancer

“…Apoptosis is associated with the occurrence and development of GC ( Frejlich et al, 2013 ). Different drugs have different mechanisms to regulate apoptosis: benzoxanthone compounds regulating the Bcl-2 related protein and the Bcl-2 protein proportion block induced gastric cancer cell apoptosis ( Fu et al, 2022 ), paclitaxel can be through the regulation of p53 gene-mediated apoptosis induced by cell signal transduction pathways ( Niapour and Seyedasli, 2022 ), cisplatin can also through the apoptosis induced by regulating the cell cycle ( Guo et al, 2022 ). Different drugs can copy a cell block in different stages, causing cells to fail to divide properly and die.…”