Synthesis, antiproliferative activities, and DNA binding of coumarin‐3‐formamido derivatives

Ten coumarin‐3‐formamido derivatives, N ‐benzyl‐coumarin‐3‐carboxamide ( 2 ), N ‐fluorobenzyl‐coumarin‐3‐carboxamide ( 3 – 5 ), N ‐methoxybenzyl‐coumarin‐3‐carboxamide ( 6 – 8 ), N ‐((1‐methyl‐1 H ‐imidazol‐5‐yl)methyl)‐coumarin‐3‐carboxamide ( 9 ), N ‐(thiophen‐2‐ylmethyl)‐coumarin‐3‐carboxamide ( 10 ), and N ‐(furan‐2‐ylmethyl)‐coumarin‐3‐carboxamide ( 11 ), were synthesized and characterized. Compound 5 crystallizes in a monoclinic system P2 1 /c space group with four chemical formulas in a unit cell; molecules of compound 5 are self‐assembled into a two‐dimensional supramolecular structure by intermolecular hydrogen bonds and C⋯C π stacking. The potential anticancer effects of these compounds on HeLa (cervical carcinoma), MCF‐7 (breast), A549 (lung), HepG2 (liver), and human umbilical vein (HUVEC) cells were examined. Compared with compounds 1 – 8 and 10 – 11 , compound 9 exhibits potent in vitro cytotoxicity against HeLa cells and lower cytotoxicity against normal cells. Therefore, further in‐depth investigations of compound 9 were performed. Absorption titration experiments and fluorescence spectroscopy studies suggested that compound 9 binds to DNA through the intercalation mode.