Synthesis And Anti-Tumor Activity Studies Of Tetrahydro-β-Carboline&Bis-Indole Compounds

Tetrahydro-β-carboline belongs to the indole alkaloids that are widely existed in nature resource. Tetrahydro-β-carboline and its derivatives have been reported to exhibit a range of biological and pharmacological activities, such as anti-tumor, anti-bacterial, anti-hypertensive and anti-Alzheimer’s. In resent years, tetrahydro-β-carboline and its derivatives have been widely concerned by their special character and structure. Bis-indole derivatives as an important class of heterocyclic compounds have become known. And they are intermediate products with biological activity in research and development and pharmaceutical industries. They can not only increase the natural metabolism of hormones in the body, but also prevent the cancer effectively. Pictet-Spengler reaction was founded by AmePictet and TheodorSpengler in1911. It has become an elegant method in the synthesis of β-carboline compounds. Besides, many complexed indole compounds are synthesized by Pictet-Spengler reaction method.In this study, a series of novel tetrahydro-β-carboline compounds were synthesized with Pictet-Spengler reaction as the key step. Indole and5-bromo-indole were used as the starting materials, which were reacted through nucleophilic addition, cyclization, reduction and Pictet-Spengler reaction etc. to accoplish the8tetrahydro-β-carboline derivatives in5to6steps with20%to25%overall yield. The synthetic approach was optimized through the different ragents, reaction temperature and reaction time etc. And target compounds were characterized by’H NMR and13C NMR. And Indole was used as the starting materials, which were reacted through Friedel-Crafts acylation, Huangminglong reaction, reduction and Pictet-Spengler reaction etc. to accoplish the6bis-indoles derivatives in4to5steps with27%to37%overall yield. The synthetic approach was optimized through the different ragents, reaction temperature and reaction time etc. Target compounds were characterized by1H NMR,13C NMR, MS and two-dimension NMR spectrograms. Among all the series,14target products and4intermediate products were synthesized, of which11compounds have not been reported yet.On this basis, the bis-indoles compounds in vitro anticancer activities were evaluated by three cancer cells:human leukemia cell K562, human hepatoma cell HepG2and human colon cancer cell HT-29. The results was2,2’-(3,3’-N-benzyl-3-1H-indol-propionamide) phenyl methane (compound13),2,2’-(3,3’-N-benzy1-3-1H-indol-propionamide) nitrophenyl methane (compound16),2,2’-(3,31-N-benzyl-3-1H-indol-propionamide) methane-fluorophenyl (compound17),2,2’-(3,3’-N-benzyl-3-1H-indol-propionamide) methane, m-methoxyphenyl (compound18) that have certain growth inhibition against K562tumor cells. The IC50was56.19μM,90.71μM,58.55μM,67.22μM. All the compounds don’t have the growth inhibition against HepG2and HT-29tumor cells. The results show that benzene ring with para weak electron-attracting group or meta electron-donating substituent have the biological activity.