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 shu

2D/3D-QSAR Studies of [1,2,4]Triazolo[1,5-a]pridinylpyridine Derivatives as Potent Anticancer Agents

a.
a. School of Pharmacy, Guangdong Medical College, Zhanjiang 524023, China;
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b. Youjiang Medical College for Nationalities, Baise 533000, China;
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c. School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China

Corresponding author: CHEN Jin-Can, XU Bi-Lian,
Received Date: 7 May 2014
Available Online: 24 September 2014
Fund Project: Supported by the National Natural Science Foundation of China (No. 20903027) (No. 20903027) the Natural Science Foundation of Guangdong Province (No. 9452402301001941) (No. 9452402301001941)

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.
- antitumor activity,
- QSAR,
- CoMFA,
- CoMSIA,
- [1,2,4]triazolo[1,5-a]pyridine
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