CuO@NiO Nanocomposite Catalyzed Synthesis of Biologically Active Indenoisoquinoline Derivatives

Indenoisoquinolines, a noncamptothecin class of synthetic compounds, show a wide range of biological activities, and some of the compounds have shown potent anticancer activity and entered into clinical trials. This stimulated the interest of medicinal chemists to develop new synthetic methodologies for the synthesis of this promising pharmacophore. In order to develop an environmentally benign synthetic method for the synthesis of indenoisoquinolines, a novel CuO@NiO nanocatalyst was prepared by simple calcination of a mixture of malachite as a sustainable copper source and nickel oxalate. The prepared nanocomposite was characterized by PXRD, FESEM, TEM, EDAX, XPS, and BET techniques. The obtained CuO@NiO nanocatalyst was used for the synthesis of indenoisoquinolines using 2-iodobenzamide and 1,3-indanedione as a starting material and ethylene glycol as a green solvent. In comparison to the reported methods, the present methodology has several advantages, such as a wide substrate scope, excellent yield, shorter reaction time, no usage of additive/base, and better values of green chemistry metrices like a low E factor (0.76), high reaction mass efficiency (56.75%), low process mass efficiency (1.76), and a high turnover number (36.69), and the catalyst was recycled up to six times without a major loss in its catalytical activity. Further, a very low-level leaching of copper ions (5.85 ppm) and nickel ions (4.83 ppm) was observed, which is much less than the tolerance limit as per WHO guidelines.