Synthesis And Cell Toxicity Activity Research In Vitro Of 2-arylisoquinolines

Isoquinoline alkaloids are existing widely in herbs, most of them have distinct biological activities, such as antitumoral, antiviral, antimicrobial, and so on. Quaternary benzo[c]phenanthridine alkaloids（QBAs） are a class of Isoquinoline alkaloids. The activity of QBAs is superior, however, the research of QBAs are limited by its shortages of species and content. According to the structure characteristics and the structure-activity relationship of the QBAs, our lab designed and synthesized a new kind of QBAs analogues, 2-aryl-3,4-dihydroisoquinolines Bromides, the bacteriostatic and acaricidal activity of which had been evaluated. Based on the previous research, we improved the route and conditions to prepare the compounds, and modifided its structure. The cytotoxic activity of the 2-aryl-3,4-dihydroisoquinolines bromides and their derivatives were evaluated.Firstly, seventeen 2-aryl-3,4-dihydroisoquinolines bromides and seventeen 1-ancyo-2-arly-1,2,3,4- tetrahydroisoquinolines were synthesized usingβ-phenethyl alcohol and poly-formaldehyde as starting materials via four and five steps, their structures were analyzed by 1H NMR, 13C NMR, ESI-MS, IR, UV.Secondly, the cytotoxic activity of twenty-nine 2-aryl-3,4-dihydroisoquinolines and six 2-phenyl-3,4-dihydroisoquinolines derivatives to Hela cell and NB4 cell were evaluated, the IC50 of seventeen 1-cyano-2-arly-1,2,3,4-tetrahydroisoquinolines were tested by MTT assay.The results showed the method was high effective, universal and convenient to synthesize related compounds; Most of the compounds showed different cytotoxic activity, and the activity of five 2-phenyl-3,4-dihydroisoquinolines derivatives were more than 2-phenyl-3,4-dihydroisoquinoline different degree. All compounds showed bettet activity against NB4 cell line than Hela cell line. The range of IC50 was 154.224-692.788μg/L, 1-cyano-2-（2’-Fluorophenyl）-1,2,3,4-tetrahydroisoquinoline provided the best cytotoxic activity against NB4 cell line（IC50 154.224μg/L）.Through the preliminary research of structure-activity relationship, we found the activity of compounds contain halogens were superior. To Hela cell line, the activity order was:—NO₂（3’,4’） >—X >—CF3 >—CH3（2’,4’） >—OH >—NH₃ >—OCH（34’）>—COOH（4’）,distinct regularity between Replace position and activity was absent; To NB4 cell line, the activity order was:—CF3（3’,4’） >—X（2’,3’） >—NO2（3’,4’） >—OH（2’,4’） >—CH3（2’,4’） >—OCH₃（4’） >—NH2 >—COO-（4’）, the activity was different when the same group in different substitution positions: the order of halogen was 2’ > 3’ > 4’ , the order of Trifluoromethyl was 3’ > 4’ > 2’. It’s potential to give more attention to these compounds on research and exploration. The mechanism of anticancer activity of the compounds can be research in order to explore the potential to be anti-cancer drugs.