In this model, n represents the number of compounds contributed to build the model. The R value is the correlation coefficient; the closer R is to 1, the better the goodness of fit of the equation. 39 The Fcalc/Fdesk value represents the ratio between the variance of the calculated and tabulated values and, therefore, indicates that the regression relationships were statistically significant and did not occur by chance. Q2 serves as a criterion of robustness and predictive ability of the regression equation. The high Q2 value (>0.5) suggests the model’s ability to give an accurate prediction. The low s (the standard error of estimates) and SPRESS values suggest that the model is statistically significant for activity prediction. 39
The brand new roentgen value of 0.976 of design six showed there is actually a powerful correlation involving the separate details (descriptors) and cytotoxic factors of xanthones. I verified one to 97.6% of the changed cytotoxic passion of your own studied xanthones was caused from the modification out of qC1, qC2, qC3, second dipole, and you will logP. Ergo, architectural amendment is recommended towards band A otherwise C. 41
The newest relationship impact showed that design 6 you may anticipate the fresh cytotoxic passion from 10 xanthone substances perfectly, that have a mountain and correlation coefficient (R 2 ) off 0
Model 6 has been used to predict the activity of the compounds to enable comparison with experimental results (observed activity). Observed versus predicted log 1/ICfifty values based on the selected model 6 are presented in Table 6, and its scatter plot is presented in Figure 1. 976 and 0.951, respectively.
The fundamental structure of xanthone (Dining table step one) suggests that phenyl band B cannot be replaced. Modification of internet costs out-of adjacent atoms (qO11, qC9, qC9a, qC4a, qO10, qC10a, and you may qC8) will only be obtained using electronic density induction out of charge modification out-of atoms inside the phenyl groups A and you can C. Based on the framework regarding compound 5 (whilst encountered the better cytotoxic passion), which customization was achieved by modifications within qC5, qC7, and you can qC8 (ring A) at qC1 and you can qC2 (band C). Therefore, these two phenyl groups need to be noticed inside the design a new xanthone with most readily useful cytotoxic pastime. 41
The best selected QSAR model is used to predict the cytotoxic activities of new synthetic xanthone compounds. The better cytotoxic activities of xanthones as IC50 values are given by the more positive value of log 1/IC50. Modification of new xanthones on the basis of katholisches Dating nur Bewertungen the selected model 6 was performed by using the structure of compound 5 (3,4,6-trihydroxyxanthone) as the model because of the highest value of the cytotoxic activity. The more negative net atomic charge of qC1, qC2, and qC3, along with the more positive value of the dipole moment and logP, was recommended to increase the more positive value of log 1/IC50. Efforts such as substitution of electron-donating groups, such as R, OH, OR, NH2, NR2, NHCOR, OCOR, or CHCR2 groups, at the C1 and C2 positions (C3 position remained unchanged as the previous structure of compound 5) could be made. Structural modifications of compound 5 generated some formulas of new xanthones with better predicted cytotoxic activities, as listed in Table 7.
Table 7 The newly designed xanthone derivatives and their predicted cytotoxic activities calculated by using the best QSAR modelAbbreviations: IC50, inhibitory concentration 50%; QSAR, quantitative structure–activity relationship.