Design, synthesis, and cytotoxic activities of isaindigotone derivatives as potential anti-gastric cancer agents

Abstract

A series of novel derivatives of isaindigotone, which comes from the root of isaits indinatca Fort, were synthesised (Compound 1 – 26 ). Four human gastrointestinal cancer cells (HCT116, PANC-1, SMMC-7721, and AGS) were employed to evaluate the anti-proliferative activity. Among them, Compound 6 displayed the most effective inhibitory activity on AGS cells with an IC 50 (50% inhibitory concentration) value of 2.2 μM. The potential mechanism study suggested that Compound 6 induced apoptosis in AGS cells. The collapse of mitochondrial membrane potential (MMP) in AGS cells was proved. In docking analysis, good affinity interaction between Compound 6 and AKT1 was discovered. Treatment of AGS cells with Compound 6 also resulted in significant suppression of PI3K/AKT/mTOR signal pathway. The collapse of MMP and suppression of PI3K/AKT/mTOR signal pathway may be responsible for induction of apoptosis. This derivative Compound 6 could be useful as an underlying anti-tumour agent for treatment of gastric cancer.

Identification of Novel Quinolone and Quinazoline Alkaloids as Phosphodiesterase 10A Inhibitors for Parkinson’s Disease through a Computational Approach

“…It showed a pi–pi interaction with Phe729 with an energy of −0.0 kcal/mol and a distance of 3.85 Å (Figure S2B). Isaindigotone (a naturally occurring vasicinone analogue) was discovered in the root of Isaits indinatca fort and has been suggested to have anticancer and anti-inflammatory therapeutic activity . It showed superior scavenging potential for superoxide generated in the hypoxanthine/xanthine oxidase system, with an IC50 of 42.2 nM.…”

“…Papaverine was used as a standard alkaloid for the PDE10A receptor. An in-house library consists of quinoline (192) and quinazoline (47) alkaloids that were subjected to docking against PDE10A, and papaverine was used as a standard. In this process, 2 quinolines and 2 quinazolines are found to be inactive against PDE10A.…”

Anti-Gastric Cancer Activity of the Cell-free Culture Supernatant of Serofluid Dish and Lactiplantibacillus plantarum YT013

“…The apoptosis was detected by fluorescent cell counts using the Annexin V Alexa Fluor 488/PI kit (Solarbio, Beijing, China) following the manufacturer’s instruction ( Du et al, 2022 ). Briefly, the AGS cells were cultured in 6-well culture plates at 8×10 5 cells/well and treated with CCS2 (0, 200, 400 and 800 μg/ml) for 48 h. After incubation, the cells were treated with trypsin without EDTA and washed twice with precooled PBS.…”

Fatty acids in cancer: Metabolic functions and potential treatment

“…It has been found that the collapse of mitochondrial membrane potential induced apoptosis in cancer cells. 98,99 Furthermore, exogenous lipids can regulate the mitochondrial membrane function, such as changing membrane permeability and affecting membrane potential. 100 For example, a large number of studies related to colon cancer have demonstrated that n-3 PUFA can effectively reduce tumorigenesis by enhancing the unsaturation of mitochondrial PLs.…”

“…Here, we will briefly discuss the relationship between mitochondria and cancer from the perspective of the mitochondrial membrane. It has been found that the collapse of mitochondrial membrane potential induced apoptosis in cancer cells 98,99 . Furthermore, exogenous lipids can regulate the mitochondrial membrane function, such as changing membrane permeability and affecting membrane potential 100 .…”