Add time:07/16/2019 Source:sciencedirect.com
Sixteen novel N-(3-carboxyl-9-benzyl-β-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 μM to about 400 μM. 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.
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