Citation:
CHEN Jin-Can, LI Guo-Dong, QIAN Li, CHEN Lan-Mei, XU Bi-Lian, ZHENG Kang-Cheng. 2D/3D-QSAR Studies of [1,2,4]Triazolo[1,5-a]pridinylpyridine Derivatives as Potent Anticancer Agents[J]. Chinese Journal of Structural Chemistry,
2014, 33(12): 1729-1740.
doi:
10.14102/j.cnki.0254-5861.2011-0365
2D/3D-QSAR Studies of [1,2,4]Triazolo[1,5-a]pridinylpyridine Derivatives as Potent Anticancer Agents
摘要:
By using a combined method of density functional theory (DFT), molecular mechanics (MM2) and statistics for two-dimensional (2D), as well as the comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) methods for three-dimensional (3D), theoretical studies on 2D/3D quantitative structure-activity relationships (QSAR) of 22 novel compounds of [1,2,4]triazolo[1,5-a] pyridinylpyridines acting as PI3K inhibitors against the human colon carcinoma cell line (HCT-116) have been performed. Both the 2D- and 3D-QSAR models established from the random 18 compounds in training set show significant statistical quality and satisfactory predictive ability (R2=0.821, q2=0.773 for 2D-QSAR, R2=0.966, q2=0.668 for CoMFA, R2=0.979, q2=0.753 for CoMSIA). The combined 2D- and 3D-QSAR studies suggest that the moderate-size, hydrophilic and electron-withdrawing group at R1 position, the bulky and hydrophobic group at R2 position, and the minor, hydrophobic, H-bond donor and electron-donating group at R3 position would enhance the anticancer activities. These obtained results help to insight into the action mechanism, and will serve as a basis for the design of new potent anticancer agents.
-
关键词:
- antitumor activity
- / QSAR
- / CoMFA
- / CoMSIA
- / [1,2,4]triazolo[1,5-a]pyridine
English
2D/3D-QSAR Studies of [1,2,4]Triazolo[1,5-a]pridinylpyridine Derivatives as Potent Anticancer Agents
Abstract:
By using a combined method of density functional theory (DFT), molecular mechanics (MM2) and statistics for two-dimensional (2D), as well as the comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) methods for three-dimensional (3D), theoretical studies on 2D/3D quantitative structure-activity relationships (QSAR) of 22 novel compounds of [1,2,4]triazolo[1,5-a] pyridinylpyridines acting as PI3K inhibitors against the human colon carcinoma cell line (HCT-116) have been performed. Both the 2D- and 3D-QSAR models established from the random 18 compounds in training set show significant statistical quality and satisfactory predictive ability (R2=0.821, q2=0.773 for 2D-QSAR, R2=0.966, q2=0.668 for CoMFA, R2=0.979, q2=0.753 for CoMSIA). The combined 2D- and 3D-QSAR studies suggest that the moderate-size, hydrophilic and electron-withdrawing group at R1 position, the bulky and hydrophobic group at R2 position, and the minor, hydrophobic, H-bond donor and electron-donating group at R3 position would enhance the anticancer activities. These obtained results help to insight into the action mechanism, and will serve as a basis for the design of new potent anticancer agents.
-
Key words:
- antitumor activity
- / QSAR
- / CoMFA
- / CoMSIA
- / [1,2,4]triazolo[1,5-a]pyridine
-
-
扫一扫看文章
计量
- PDF下载量: 0
- 文章访问数: 1667
- HTML全文浏览量: 70
下载:
