Synthesis, characterization, anti‐proliferative evaluation, and molecular docking study of some new N‐(1, 3‐dioxoisoindolin‐4‐yl)acetamide derivatives

Abstract

AbstractA series of new N‐(1,3‐dioxoisoindolin‐4‐yl)acetamide derivatives were designed and synthesized via a condensation reaction between N‐(1,3‐dioxo‐1,3‐dihydro isobenzofuran‐4‐yl)acetamide and various aliphatic and aromatic amines in water as an environmentally friendly solvent. All synthesized compounds (NPD 1–14) molecular structure was confirmed by their FTIR, 1H NMR, 13C NMR, and mass spectroscopy. The final target compounds were screened for their in vitro antiproliferative activity by taking 5‐Fluorouracil (5‐FU) as a reference drug. Among 14 newly synthesized compounds, five compounds were shown to be effectively cytotoxic against the MCF7 cells. In comparison to the standard medication drug 5‐FU (CC50 = 11.219 ± 0.847), the synthesized compounds NPD‐8 (CC50 = 16.14 ± 2.08 μM) and NPD‐12 (CC50 = 11.26 ± 1.158 μM) demonstrated the most active against the MCF7 cells. Furthermore, in silico study was performed to find molecular level interaction of active compounds with anticancer drug target enzyme NUDT5 inhibitors block hormone signaling in breast cancer cells. The compound NPD‐12 showed the highest molecular binding energy −8.3 kcal/mol which interacted more effectively than the reference drug 5‐FU binding energy −4.6 kcal/mol. These synthesized N‐(1,3‐dioxoisoindolin‐4‐yl) acetamide derivatives have been identified as a potential class of chemicals for further research as plausible new anticancer entities.