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 roentgen worth of 0.976 regarding model 6 presented that there is actually a strong relationship amongst the separate variables (descriptors) and you may cytotoxic things of one’s xanthones. We verified you to definitely 97.6% of altered https://datingranking.net/pl/eastmeeteast-recenzja/ cytotoxic activity of your own learned xanthones are brought about from the amendment off qC1, qC2, qC3, moment dipole, and logP. These types of findings had been highly relevant to an earlier investigation one to indicated that structural modification of aromatic ring C, specifically at C1 and you can C2 ranks, predicted improve of your cytotoxic passion of the xanthone substances. Thus, structural modification is suggested with the ring A great otherwise 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 0.976 and 0.951, respectively.
The fundamental build out of xanthone (Desk step one) demonstrates phenyl ring B cannot be substituted. Customization of your own net charges of surrounding atoms (qO11, qC9, qC9a, qC4a, qO10, qC10a, and qC8) simply be obtained because of electronic density induction from fees modification off atoms in phenyl bands A great and you will C. On the basis of the structure away from compound 5 (since it encountered the better cytotoxic craft), that it adjustment would-be achieved by adjustment within qC5, qC7, and qC8 (band A good) as well as qC1 and you may qC2 (ring C). Therefore, those two phenyl groups should be experienced during the designing a special xanthone that have most useful cytotoxic craft. 41
Amendment of new xanthones according to the picked design 6 try did utilising the construction out-of compound 5 (step 3,cuatro,6-trihydroxyxanthone) once the model because of the higher value of this new cytotoxic craft
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.
