Cyano-2-oxopyridines: Green synthesis, cytotoxicity evaluation and molecular docking study

Abstract

An efficient four-component and one-pot synthesis of 1,6-diamino-3,5-dicyano-2-oxopyridine compounds were investigated in the presence of three catalysts such as bulk and nanosheet graphitic carbon nitride and IS@SMNPs (piperazinium ionic salt attached on silica-coated magnetic nanoparticle) as recyclable heterogeneous catalysts. From the results, the magnetic nanocatalyst was the best among examined catalysts. The highest yield (85%) and the shortest reaction time (40 min) were obtained (for the four-component reaction between benzaldehyde, malononitrile, ethyl cyanoacetate and hydrazine hydrate) in the presence of 50 mg of‏ ‏IS@SMNPs at room temperature. Recycling of IS@SMNPs was tested, and after the fifth cycle, 80% yield was obtained. Good yields in a short time, simple recycling, and being environmentally friendly are advantages of the magnetic catalyst. MTT assay screened the cytotoxicity of 6a, 6b, 6e, and 6h derivatives against two carcinoma cell lines, such as HeLa and MCF-7 (estrogen receptor-dependent). 6h and 6b exhibited the most potent cytotoxicity, respectively, and 6b showed the lowest one against both cell lines. The interactions of selected derivatives and Genistein (an estrogen receptor inhibitor) in the active site of estrogen receptor-α were predicted using molecular docking. The docking results of synthetic compounds illustrated similar interactions to redocked Genistein in the active site, and compounds 6e and 6h had the highest binding affinity.