Synthesis Of Safrole Oxide Derivatives And Antiproliferative Effects On A549 Human Lung Cancer Cells

The safrole derivatives, 1-(benzo[d][1,3]dioxol-5-yl)-3-((4-nitrophenyl)(phenyl) amino)ropan-2-ol (9a), 1-(benzo[d][1,3]dioxol-5-yl)-3-(o-tolylamino)propan-2-ol (9b), 1-(benzo[d][1,3]dioxol-5-yl)-3-((4-nitrophenyl)amino)propan-2-ol (9c),3-(benzo[d] [1,3]dioxol-5-yl)-2-((4-methoxyphenyl)amino)propan-l-ol (11a),3-(benzo[d] [1,3] dioxol-5-yl)-2-((2-methoxyphenyl)amino)propan-l-ol (11b),3-(benzo[d][1,3]dioxol-5-yl)-2-(o-tolylamino)propan-l-ol (11c), (E)-5-(3-ethoxyprop-1-en-1-yl)benzo [d] [1,3]dioxole (14a), (E)-5-(3-propoxyprop-l-en-1-yl)benzo[d][1,3]dioxole(14b), (E)-5-(3-butoxyprop-l-en-1-yl)benzo[d][1,3]dioxole (14c), (E)-5-(3-(pentyloxy)prop-1-en-1-yl)benzo[d][1,3]dioxole (14d), (E)-5-(3-(hexyloxy)prop-1-en-1-yl)benzo[d] [1,3] dioxole (11e), (E)-5-(3-(benzyloxy)prop-l-en-1-yl)benzo[d][1,3]dioxole(14f), (E)-5-(3-((4-methylbenzyl)oxy)prop-l-en-1-yl)benzo[d][1,3]dioxole (14g), (E)-5-(3-((3-methylbenzyl)oxy) prop-1-en-1-yl)benzo[d][1,3]dioxole (14h), safrole oxide (8) and (E)-3-(benzo[d][1,3] dioxol-5-yl)prop-2-en-l-ol (12) were synthesized by using safrole as starting material. The antiproliferative activity of these compounds on A549 human lung cancer cells were assayed and compared with control compounds. Furthermore, the structure-activity relationship (SAR) was discussed. All the desired compounds were prepared from commercial materials in moderate to good yields, and they were characterized by 1H NMR, 13C NMR and HRMS.In the reactions, safrole derivatives 9a-c, lla-c, and 14a-h were synthesized by the reaction of safrole oxide with aniline, or its alkyl allyl ether derivative with alkyl bromide in moderate to good yields.The antiproliferative activity was tested by MTT assay. The antiproliferative effects of all the target molecules on A549 cell growth were investigated and it was found that the synthesized compounds could suppress A549 lung cancer cell growth.