Novel N-(3-carboxyl-9-benzyl-β-carboline-1-yl)ethylamino acids: Synthesis, anti-tumor evaluation, intercalating determination, 3D QSAR analysis and docking investigation

Sixteen novel N-(3-carboxyl-9-benzyl-beta-carboline-1-yl)ethylamino acids (6a-p) were synthesized as intercalating lead compounds. In the in vitro cytotoxic assay their IC50 values against five human carcinoma cell lines ranged from 10.95 mu M to about 400 mu M. On S180 mouse model eight of them exhibited anti-tumor action, four of them showed the same anti-tumor potency as that of cytarabine. The preliminary toxicity evaluation revealed that the LD50 values of 6a-p should be more than 500 mg/kg. With CT DNA as model system an intercalating mechanism was explored. Using 3D QSAR analysis the relationship of the in vivo anti-tumor activity and the structure was quantitatively described. By docking 6a-p onto d(CGATCG)(2) oligonucleotides the intercalation was demonstrated. (C) 2009 Elsevier Masson SAS. All rights reserved.