A one-pot route to novel 3-{1-([5-amino-7-(arylamino)-6-cyano-7H-[1,4]oxaphosphinino[2,3-d]thiazol-2-yl]hydrazinyl)ethylidene}-2H-chromen-2-one: Synthesis, cytotoxic activities, apoptosis, and cell cycle studies

An innovative and efficient one-pot approach has been established for the synthesis of 3-{1-([5-amino-7-(arylamino)-6-cyano-7H-[1,4]oxaphosphinino[2,3-d]thiazol-2-yl]hydrazinyl)ethylidene}-2H-chromen-2-one (2a-h) using aromatic amine, phosphorus trichloride, malononitrile, and 3-{[1-(4-oxo-5H-thiazol-2-yl)hydrazinyl]ethylidene}-2H-chromen-2-one with triethylamine. This method is efficient and straightforward, offering high yields, easy product isolation, and minimal waste. The cytotoxic properties against PC3, LS174T, and HepG2 cancer cell lines revealed promising activity for compounds 2d and 2e (fluorine and chlorine substitutions), comparable to Tivozanib. Flow cytometry indicated that these bioactive compounds significantly increased late apoptosis and halted cell cycle progression at S and G2 phases, demonstrating their potential as anticancer agents. Both compounds 2d and 2e were then subjected to a molecular docking experiment to see how they bind with VEGFR-2 receptor.