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 new r worth of 0.976 away from model 6 displayed that there was an effective correlation between your independent parameters (descriptors) and cytotoxic products of one’s xanthones. We confirmed one to 97.6% of your own altered cytotoxic hobby of your own studied xanthones is actually triggered from the modification away from qC1, qC2, qC3, minute dipole, and you may logP. Such conclusions was indeed connected to an earlier analysis one to showed that structural modification of one’s fragrant band C, especially at C1 and you can C2 positions, forecast improvement of your own cytotoxic passion of one’s xanthone ingredients. Thus, structural modification is suggested to the ring A or C. 41
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. The correlation result showed that model 6 could predict the cytotoxic activity of 10 xanthone compounds very well, with a slope and correlation coefficient (R 2 ) of 0 charmdate.976 and 0.951, respectively.
The fundamental framework from xanthone (Desk step 1) suggests that phenyl band B cannot be substituted. Customization of the internet costs out-of adjoining atoms (qO11, qC9, qC9a, qC4a, qO10, qC10a, and you can qC8) only be bought compliment of electronic occurrence induction off charge modification regarding atoms during the phenyl groups A good and you can C. Using the framework of material 5 (because met with the better cytotoxic passion), that it modification might be accomplished by adjustment at qC5, qC7, and qC8 (band A beneficial) and at qC1 and you can qC2 (band C). Therefore, both of these phenyl bands should be experienced for the creating a unique xanthone which have most useful cytotoxic interest. 41
Amendment of brand new xanthones using the chosen model six try performed using the build away from material 5 (step 3,4,6-trihydroxyxanthone) due to the fact model by the high property value the cytotoxic activity
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. 50. 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.