biostudies-literatureDu KThe College Students’ innovation and entrepreneurship training program of Lanzhou Universitythe Key Research and Development Program of Gansu Provincethe Technological Innovation Guidance Program of Gansu Provincethe Key Program for International S&T Cooperation Projects of China Gansu Province1212-1226https://www.ebi.ac.uk/biostudies/studies/S-EPMC9037217biostudies-literatureUnknown37(1)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 IC50 (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 significJournal of enzyme inhibition and medicinal chemistryDesign, synthesis, and cytotoxic activities of isaindigotone derivatives as potential anti-gastric cancer agents.PMC903721718YF1WA11521CX6QA12721YF5FA112Liu HHu SChen PZhang HMa YZhu HYang CMa WZhou ZLiu YTian YJiang XDu KfalseDesign, synthesis, and cytotoxic activities of isaindigotone derivatives as potential anti-gastric cancer agents.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 IC50 (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 signific2022-01-01T00:00:00Z2022 Dec2026-05-30T15:48:26.915Z2025-04-04T10:02:33.573ZS-EPMC90372173545049910.1080/14756366.2022.2065672