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 new r property value 0.976 regarding model six presented that there was a powerful correlation between your independent details (descriptors) and you can cytotoxic activities of one’s xanthones. I confirmed you to 97.6% of your changed cytotoxic activity of the studied xanthones try triggered from the amendment out of qC1, qC2, qC3, time dipole, and you will logP. Therefore, structural amendment is recommended towards the band A great or C. 41
Brand new relationship effect indicated that design six you may anticipate this new cytotoxic interest away from ten xanthone substances well, that have a slope and you may correlation coefficient (Roentgen 2 ) from 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.
Might design from xanthone (Dining table step 1) suggests that phenyl band B can not be replaced. Alteration of websites fees away from surrounding atoms (qO11, qC9, qC9a, qC4a, qO10, qC10a, and qC8) simply be bought because of digital occurrence induction out-of charge modification out of atoms for the phenyl bands A and C. According to the construction away from substance 5 (whilst met with the better cytotoxic pastime), which adjustment might possibly be achieved by modifications at qC5, qC7, and you can qC8 (ring An excellent) and also at qC1 and you may qC2 (ring C). For this reason, these two phenyl rings have to be noticed inside the making yet another xanthone which have most useful cytotoxic interest. 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.