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/Fdining table 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 out-of model six displayed there try an effective relationship within independent variables (descriptors) and cytotoxic facts of xanthones. I verified one to 97.6% of your own changed cytotoxic hobby of the read xanthones is brought about because of the amendment out-of qC1, qC2, qC3, second dipole, and you can logP. Therefore, structural modification is suggested into band Good or C. 41
This new correlation influence indicated that design six you can expect to predict the newest cytotoxic craft out-of ten xanthone compounds really well, that have a slope and you can relationship coefficient (Roentgen dos ) out-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/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 design out of xanthone (Desk step one) indicates that phenyl band B can not be replaced. Alteration of your own web charge of adjoining atoms (qO11, qC9, qC9a, qC4a, qO10, qC10a, and you may qC8) simply be bought owing to digital density induction away from charge amendment out of atoms into the phenyl bands A beneficial and you can C. On the basis of the build out of substance 5 (whilst met with the top cytotoxic activity), that it modification could well be attained by improvement at the qC5, qC7, and you may qC8 (band Good) and also at qC1 and qC2 (band C). For this reason, these phenyl bands should be considered for the designing a separate xanthone having finest 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 https://www.datingranking.net/es/citas-de-viaje/ activities calculated by using the best QSAR modelAbbreviations: IC50, inhibitory concentration 50%; QSAR, quantitative structure–activity relationship.