In this model, n represents the number of compounds contributed to build the model. The R value is the correlation coefficient; the closer Liste der amerikanischen neuen Dating-Seiten R is to 1, the better the goodness of fit of the equation. 39 The Fcalc/Ftable 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
This new r value of 0.976 off design 6 demonstrated there is actually an effective relationship between the independent variables (descriptors) and you will cytotoxic things of xanthones. We confirmed one to 97.6% of your changed cytotoxic activity of the learnt xanthones is actually triggered of the modification out of qC1, qC2, qC3, minute dipole, and logP. Therefore, architectural modification is recommended on the ring A great otherwise C. 41
Brand new correlation influence showed that design 6 you will definitely assume new cytotoxic passion out-of 10 xanthone ingredients really well, that have a hill and you can relationship coefficient (Roentgen dos ) regarding 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 basic structure away from xanthone (Dining table 1) reveals that phenyl band B cannot be replaced. Adjustment of one’s online charges out-of adjacent atoms (qO11, qC9, qC9a, qC4a, qO10, qC10a, and you can qC8) will be bought as a result of electronic density induction out-of fees modification out of atoms in the phenyl rings An effective and you will C. According to the framework regarding compound 5 (because it met with the better cytotoxic passion), this adjustment might possibly be accomplished by improvement on qC5, qC7, and you can qC8 (ring A great) and also at qC1 and you can qC2 (ring C). Ergo, these phenyl bands need to be experienced inside design a different xanthone having most readily useful cytotoxic craft. 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 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.
