Three-dimensional quantitative structure activity relationship （3D-QSAR） and docking studies of a series of arylthioindole derivatives as tubulin inhibitors against human breast cancer cell line MCF-7 have been carr...Three-dimensional quantitative structure activity relationship （3D-QSAR） and docking studies of a series of arylthioindole derivatives as tubulin inhibitors against human breast cancer cell line MCF-7 have been carried out. An optimal 3D-QSAR model from the comparative molecular field analysis （CoMFA） for training set with significant statistical quality （R2=0.898） and predictive ability （q2=0.654） was established. The same model was further applied to predict pIC50 values of the compounds in test set, and the resulting predictive correlation coefficient R2（pred） reaches 0.816, further showing that this CoMFA model has high predictive ability. Moreover, the appropriate binding orientations and conformations of these compounds interacting with tubulin are located by docking study, and it is very interesting to find the consistency between the CoMFA field distribution and the 3D topology structure of active site of tubulin. Based on CoMFA along with docking results, some important factors improving the activities of these compounds were discussed in detail and were summarized as follows： the substituents R3-R5 （on the phenyl ring） with higher electronegativity, the substituent R6 with higher eleetropositivity and bigger bulk, the substituent R7 with smaller bulk, and so on. In addition, five new compounds with higher activities have been designed. Such results can offer useful theoretical references for experimental works.展开更多
Theoretical study on the electronic structures and related properties of 2,2,6,6-tetramethyl- l-piperidinyloxy （TEMPO） and its cationic lipid derivates in the charge/discharge processes has been carried out using th...Theoretical study on the electronic structures and related properties of 2,2,6,6-tetramethyl- l-piperidinyloxy （TEMPO） and its cationic lipid derivates in the charge/discharge processes has been carried out using the density functional theory （DFT） at the （U）B3LYP/6-31G（d,p） or 6-31＋G（d,p） level. The changes and regularities of geometric and electronic properties of these compounds in the charge/discharge processes were revealed in detail. The compu- tational results show that the substitute group plays a very important role in the electronic structures and related properties of TEMPOs during the charge/discharge processes. It is very interesting to find that after getting an electron, TEMPO is more stable in singlet state but the lipid is more stable in triplet state. For TEMPO, both the charge and the discharge processes greatly influence the electronic properties of N and O atoms of the radical part. For the cationic lipid, the discharge process mainly influences the pyridinium head and the charge process mainly influences the free radical head. Moreover, the solvent effect plays an important role in some bond lengths and the charge population of the free radical head. In addition, the UV-Vis absorption spectra simulated using TDDFT at the 6-31G（d,p） with the experimental ones. of TEMPO and the lipid were calculated and or 6-31＋G（d,p） level, in satisfying agreement展开更多
基金This work was supported by the National Natural Science Foundation of China （No.20673148）. We heartily thank the Molecular Discovery Ltd. for giving us the Dock 6.0 program as a freeware and the College of Life Sciences, Sun Yat-Sen University for the SYBYL 6.9 computation environment support.
文摘Three-dimensional quantitative structure activity relationship （3D-QSAR） and docking studies of a series of arylthioindole derivatives as tubulin inhibitors against human breast cancer cell line MCF-7 have been carried out. An optimal 3D-QSAR model from the comparative molecular field analysis （CoMFA） for training set with significant statistical quality （R2=0.898） and predictive ability （q2=0.654） was established. The same model was further applied to predict pIC50 values of the compounds in test set, and the resulting predictive correlation coefficient R2（pred） reaches 0.816, further showing that this CoMFA model has high predictive ability. Moreover, the appropriate binding orientations and conformations of these compounds interacting with tubulin are located by docking study, and it is very interesting to find the consistency between the CoMFA field distribution and the 3D topology structure of active site of tubulin. Based on CoMFA along with docking results, some important factors improving the activities of these compounds were discussed in detail and were summarized as follows： the substituents R3-R5 （on the phenyl ring） with higher electronegativity, the substituent R6 with higher eleetropositivity and bigger bulk, the substituent R7 with smaller bulk, and so on. In addition, five new compounds with higher activities have been designed. Such results can offer useful theoretical references for experimental works.
文摘Theoretical study on the electronic structures and related properties of 2,2,6,6-tetramethyl- l-piperidinyloxy （TEMPO） and its cationic lipid derivates in the charge/discharge processes has been carried out using the density functional theory （DFT） at the （U）B3LYP/6-31G（d,p） or 6-31＋G（d,p） level. The changes and regularities of geometric and electronic properties of these compounds in the charge/discharge processes were revealed in detail. The compu- tational results show that the substitute group plays a very important role in the electronic structures and related properties of TEMPOs during the charge/discharge processes. It is very interesting to find that after getting an electron, TEMPO is more stable in singlet state but the lipid is more stable in triplet state. For TEMPO, both the charge and the discharge processes greatly influence the electronic properties of N and O atoms of the radical part. For the cationic lipid, the discharge process mainly influences the pyridinium head and the charge process mainly influences the free radical head. Moreover, the solvent effect plays an important role in some bond lengths and the charge population of the free radical head. In addition, the UV-Vis absorption spectra simulated using TDDFT at the 6-31G（d,p） with the experimental ones. of TEMPO and the lipid were calculated and or 6-31＋G（d,p） level, in satisfying agreement
