Such results was connected to an earlier analysis you to showed that structural amendment of your own aromatic ring C, particularly in the C1 and C2 positions, forecast improvement of your own cytotoxic passion of the xanthone substances
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/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
The fresh new r property value 0.976 from design six demonstrated that there is actually a strong relationship within independent parameters (descriptors) and cytotoxic issues of one’s xanthones. We verified you to 97.6% of changed cytotoxic interest of one’s studied xanthones is actually caused of the modification from qC1, qC2, qC3, time dipole, and you may logP. Ergo, structural amendment is recommended on band A great otherwise C. 41
The correlation impact revealed https://datingranking.net/de/insassendatierung/ that design 6 you can expect to predict the fresh new cytotoxic hobby of ten xanthone ingredients really well, which have a hill and you may correlation coefficient (R 2 ) of 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/IC50 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 essential structure of xanthone (Dining table step 1) demonstrates phenyl band B can’t be substituted. Alteration of one’s online costs of adjoining atoms (qO11, qC9, qC9a, qC4a, qO10, qC10a, and you may qC8) will simply be obtained through electronic thickness induction of charge modification regarding atoms inside phenyl rings A great and you can C. Using the design off substance 5 (because it met with the better cytotoxic pastime), this modification might possibly be achieved by modifications within qC5, qC7, and you can qC8 (band A good) and at qC1 and you can qC2 (ring C). Ergo, these phenyl bands should be considered in the design an alternative xanthone having better cytotoxic passion. 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.