Abstract: The quantitative structure-activity relationship(QSAR) of indolo[1,2-b] quinazoline derivatives, in regard to their antitumor activity, was systematically studied using the density functional theory(DFT), molecular mechanism (MM＋) and regression analysis methods. via a stepwise regression analysis, some main independent factors affecting the activity of the compounds were selected out, and then the QSAR equation was established. It has been found that the energy difference (ΔεL-H) between the lowest unoccupied molecular orbital (LUMO) and the highest occupied molecular orbital (HOMO) of the compound, the hydrophobic parameter (lgP) of the molecule, as well as the total net charge (ΣQD) of the D-ring skeleton and the net charge(QFR1) of the first atom of the substituent R1 on D-ring are the main independent factors contributing to the antitumor activity of the compound. The cross-validation rcv2 and the fitting correlation coefficient r2 for the model established by this study are 0.7364 and 0.8505, respectively. The results suggest that this model has good predictability and further indicate that the LUMO energy closely relative to ΔεL-H and the conjugative planarity area play a very important role in the DNA-binding and the activity of the compounds. Therefore, some higher antitumor active compounds can be designed prior to their synthesis via selecting some substituents (R1), which have stronger electron-withdrawing ability and can form greater conjugative planarity area with the skeletons of the series of the compounds.

Key words: Indolo[2,1-b]quinazoline, Antitumor activity, Quantum chemistry, 　Density functional theory(DFT), Quantitative structure-activity relationship(QSAR)