These types of findings was basically highly relevant to an earlier analysis you to definitely showed that structural amendment of one’s fragrant band C, specifically at C1 and you will C2 ranks, predicted improve of your own cytotoxic hobby of 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/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 latest roentgen worth of 0.976 regarding design 6 showed that there try an effective correlation within independent parameters (descriptors) and cytotoxic situations of one’s xanthones. We confirmed you to definitely 97.6% of the changed cytotoxic activity of learnt xanthones is actually triggered from the modification regarding qC1, qC2, qC3, second dipole, and logP. For this reason, structural modification is suggested towards the band A great or C. 41
The newest relationship result indicated that model six you will anticipate the cytotoxic craft of ten xanthone ingredients very well, having a hill and you can relationship coefficient (Roentgen 2 ) 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 BHM Dating Reviews wollen 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 design out-of xanthone (Desk step 1) shows that phenyl ring B can not be replaced. Adjustment of the websites fees off surrounding atoms (qO11, qC9, qC9a, qC4a, qO10, qC10a, and qC8) simply be purchased as a result of digital thickness induction out-of costs amendment out-of atoms in phenyl rings A and you can C. In line with the design off substance 5 (whilst encountered the best cytotoxic interest), so it customization would be accomplished by modifications in the qC5, qC7, and you may qC8 (band A beneficial) as well as qC1 and you will qC2 (band C). Therefore, those two phenyl groups must be thought into the creating another type of xanthone with ideal cytotoxic activity. 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.