Design and Synthesis of Some Novel Phosphorus Heterocycles-Based Coumarin Derivatives as Promising Anticancer Agents

Abstract

An efficient method was developed for the synthesis of eight novel functionalized 1,2,4,3-triazaphospholes and one 1,3,2-thiazaphosphinine incorporating a coumarin ring. Additionally, two interesting examples of diethyl coumarinyl phosphonate and diethyl chromeno-[3,4-c][1,2,4]triazolo[4,3-a]pyridinyl phosphonate were obtained. The proposed methodology involved the treatment of N'-benzoyl-2-oxo-2H-chromene-3-carbohydrazonamide (2) with various phosphorus agents, including phosphorus halides, phosphorus triamide, phosphorus esters, and phosphorus sulfides. IR, NMR, and mass spectrometric methods were used to confirm the structures of the prepared compounds. The antiproliferative properties of the isolated compounds were screened against HepG-2, MCF-7, and A549 cancer cells. The products 5, 7, 9, and 10 exhibited excellent cytotoxic properties compared with doxorubicin. These four bioactive compounds have low toxicity in healthy human HFB4 cells.