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3D-QSAR Studies on Thiazolidin-4-one S1P1 Receptor Agonists by CoMFA and CoMSIA
College of Biology Science and Technology, Jinan University, Guangzhou 510632, China
Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, China
Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China
* Author to whom correspondence should be addressed.
Received: 12 July 2011; in revised form: 2 September 2011 / Accepted: 5 September 2011 / Published: 28 September 2011
Abstract: Selective S1P1 receptor agonists have therapeutic potential to treat a variety of immune-mediated diseases. A series of 2-imino-thiazolidin-4-one derivatives displaying potent S1P1 receptor agonistic activity were selected to establish 3D-QSAR models using CoMFA and CoMSIA methods. Internal and external cross-validation techniques were investigated as well as some measures including region focusing, progressive scrambling, bootstraping and leave-group-out. The satisfactory CoMFA model predicted a q2 value of 0.751 and an r2 value of 0.973, indicating that electrostatic and steric properties play a significant role in potency. The best CoMSIA model, based on a combination of steric, electrostatic, hydrophobic and H-bond donor descriptors, predicted a q2 value of 0.739 and an r2 value of 0.923. The models were graphically interpreted using contour plots which gave more insight into the structural requirements for increasing the activity of a compound, providing a solid basis for future rational design of more active S1P1 receptor agonists.
Keywords: CoMFA; CoMSIA; QSAR; thiazolidin-4-one; S1P1 receptor agonists
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Qian, C.; Zheng, J.; Xiao, G.; Guo, J.; Yang, Z.; Huang, L.; Chao, W.; Rao, L.; Sun, P. 3D-QSAR Studies on Thiazolidin-4-one S1P1 Receptor Agonists by CoMFA and CoMSIA. Int. J. Mol. Sci. 2011, 12, 6502-6516.
Qian C, Zheng J, Xiao G, Guo J, Yang Z, Huang L, Chao W, Rao L, Sun P. 3D-QSAR Studies on Thiazolidin-4-one S1P1 Receptor Agonists by CoMFA and CoMSIA. International Journal of Molecular Sciences. 2011; 12(10):6502-6516.
Qian, Chuiwen; Zheng, Junxia; Xiao, Gaokeng; Guo, Jialiang; Yang, Zhaoqi; Huang, Li; Chao, Wei; Rao, Longyi; Sun, Pinghua. 2011. "3D-QSAR Studies on Thiazolidin-4-one S1P1 Receptor Agonists by CoMFA and CoMSIA." Int. J. Mol. Sci. 12, no. 10: 6502-6516.