3D quantitative structure-activity relationships study on anti-gastric cancer of chrysin derivatives

In this paper, 3D-QSAR models were constructed to conduct a preliminary study on the structure-activity relationship of chrysin. The three-dimensional structures of the selected 54 chrysin derivatives were constructed by SYBYL-X 2.0 software, molecular mechanics procedures for conformational optimization, and molecular alignment. The 3D-QSAR model of these compounds was constructed by comparative molecular force field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA), and the structure-activity relationships of chrysin compounds was preliminarily discussed. CoMFA and CoMSIA models are all constructed reasonably and reliably (CoMFA: q(2) = 0.703, r(2) = 0.886, SEE = 0.217, F = 113.572; CoMSIA: q(2) = 0.647, r(2) = 0.841, SEE = 0.255, F = 111.740), a series of three-dimensional contour maps were obtained to visualize the influence of various fields around the compound molecules on the drug activity. Groups with more hydrogen bonding acceptors attached to the end of the 7-O-alkane chain of chrysin are favorable for the molecular activity, such as amino acids. However, excessively long 7-O-alkane chains or the introduction of bulky hydrophobic groups on the 7-O-alkane chain will reduce the activity of the molecule. In contrast, the introduction of bulky hydrophobic groups on the side chains of amino acids will enhance the molecular activity.

Automated summary

In this study, 3D-QSAR models were constructed to investigate the structure-activity relationship of chrysin. The structures of 54 chrysin derivatives were constructed using SYBYL-X 2.0 software, and the models were built using CoMFA and CoMSIA methods. The results showed that certain groups attached to the 7-O-alkane chain of chrysin, such as amino acids, enhance its activity, while excessively long chains or bulky hydrophobic groups reduce the activity. On the other hand, the introduction of bulky hydrophobic groups on the side chains of amino acids increases the activity of the molecule.