Synthesis And Biological Evaluation Of Novel Coumarin Derivatives With Anti-tumor Activity

Coumarin derivatives that possess the activity of anti-arrhythmic, anti-clotting, antiosteoporosis, anti-oxidant, analgesic, anti-hypertensive, and asthma, photosensitive and anti-HIV, antitumor, and other biological activities, have great potential Med. value. Thus, We incorporated some different bioactive units, such as dithiocarbamate (DTC), sulfonamide, thioether, piperazine and other active substructure unit into the coumarin framework based on the connecting principle of actively biological groups. There were two types of coumarin derivatives been designed and synthesized. All the target compounds were characterized by1HNMR, MS and elemental analysis.(1) DTC and arylsulfonamide coumarin derivatives. By modifying the N atom of7-(N-coumarin) arylsulfonamides with bromoethyl and introducing dithiocarbamate unit or heterocycle unit into the substituted coumarin ring, we got17novel compounds, which were then tested for their cytotoxic activity against A549cell line by MTT assay. The results indicated that most of the target compounds were found to be weakly cytotoxic against A549cell line, and only compounds Y11190、Y11192、Y11199exhibited some cytotoxic activity, with the cell livability being68.42%,53.00%and51.15%when the concentration increased to10.0μM, respectively. These compounds with the piperidine ring or methyl-1,3,4-thiadiazole showed a certain degree of cytotoxicity on the tumor cell.(2) DTC and piperazine coumarin derivatives. A set of novel Aryl4-(2-oxo-2H-chromen-4-yl)piperazine-l-carbodithioate derivatives were synthesized by introducing DTC and piperazine units to benzopyran-2-one nucleus at C-4position, and we got34novel compounds. The cytotoxic activity test showed that this series of compounds highlighted the substituents on C-6positions, which had some effects on their cytotoxic activity. When the coumarin ring was without any substituents or was replaced by some electron-withdrawing groups such as chlorine or flurine on its C-6positions, these compounds showed good rather than excellent cytoxic activityies, eg. compounds Y11208, Y12129-Y12132, with their IC50、10.0μM. When the coumarin ring was replaced by some electron-donating groups such as methyl or methoxyl on its C-6positions, their cytoxic activity against A549cell line were significantly increased, the cell apoptosis induced by the derivatives was especially significant when the substituent was a methyl group, with the representive compounds Y12123and Y12126showed their IC50ranging from0.1μM to1.0μM.