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.