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Int J Mol Sci. 2011;12(10):6502-16. doi: 10.3390/ijms12106502. Epub 2011 Sep 28.

3D-QSAR studies on thiazolidin-4-one S1P₁receptor agonists by CoMFA and CoMSIA.

Author information

1
College of Biology Science and Technology, Jinan University, Guangzhou 510632, China; E-Mails: litmony@sohu.com (C.Q.); thuangli@jnu.edu.cn (L.H.).

Abstract

Selective S1P(1) receptor agonists have therapeutic potential to treat a variety of immune-mediated diseases. A series of 2-imino-thiazolidin-4-one derivatives displaying potent S1P(1) 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 q(2) value of 0.751 and an r(2) 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 q(2) value of 0.739 and an r(2) 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 S1P(1) receptor agonists.

KEYWORDS:

CoMFA; CoMSIA; QSAR; S1P1 receptor agonists; thiazolidin-4-one

PMID:
22072901
PMCID:
PMC3210992
DOI:
10.3390/ijms12106502
[Indexed for MEDLINE]
Free PMC Article

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