To discover the anti-tumoral indoles a series of benzyl 1,2,3,5,11,11a-hexahydro-3,3-dimethyl-1-oxo-6H-imidazo[3',4':1,2]pyridin[3,4-b]indole-2-substituted acetates (2a-n) are prepared via one-pot-preparation. The IC(50) values of 2a-n in vitro against human lung carcinoma, prostate cancer, nasopharyngeal carcinoma, vincristine-resistant KB subline and human breast carcinoma cells range from 40 nM to 60 microM. On Sarcoma 180 (S180) tumor-bearing mouse model four of them (2e,g,h,i) significantly inhibited the tumor growth. At the dose of 0.1mg/kg the efficacy of the most potent 2h was equal to that of 1.0mg/kg of doxorubicin. In contrast to doxorubicin, at 1.0mg/kg of dose 2e,g,h,i did not induce the treated S180 mice to have organ atrophy and body emaciation. The healthy mice receiving 10, 100 and 500 mg/kg of 2e,g,h,i gave no any neurotoxic response. Even up to the dose of 500 mg/kg the healthy mice occurred no death. The interaction of 2a-n with DNA was confirmed by the fluorescence quenching experiments and automated flexible ligand docking. By 3D QSAR analysis the IC(50) values of 2a-n against prostate cancer cells were correlated with the structures and conformations of their side chains. To increase the data related to their physical-chemical properties the experimental LogP values were also provided.