Benchmarking the distribution coefficient of anticancer lead compounds using the predicted log D values of clinically approved chemotherapeutic drugs

Abstract

BACKGROUND: The distribution coefficient (Log D) can predict the solubility of a compound at a particular pH. In identifying lead compounds, Log D is helpful to predict the behavior, permeability, and clearance of a compound in the different organs. AIM AND OBJECTIVE: This study examined the ability of Log D to discriminate cancer tissues from non-cancer tissues using the predicted Log D of various clinically approved anticancer drugs. MATERIALS AND METHODS: We collected the information on the different anticancer drugs for breast, liver, kidney, lung small, lung non-small, prostate, and bone cancer from the National Cancer Institute. We predicted their Log D values at different pH of their respective tissues. RESULTS: Results show that only the Log D values of breast and lung non-small cancer drugs in the cancer tissues were significantly different (p<0.05) from the Log D of the non-cancer tissue counterpart. Moreover, the Log D value of the normal and bone cancer tissues is significantly different (p<0.05) from the different normal and cancer tissues evaluated. Furthermore, the Log D values of small lung cancer tissues are significantly different (p<0.05) from normal and kidney cancer tissues, normal and liver cancer tissues, and normal non-small and lung cancer tissues. CONCLUSION: These findings suggest that drugs that may be permeable in breast and lung non-small cancer tissues may not be permeable in their normal tissue counterpart. Additionally, bone and lung small cancer drugs may have low permeability with other tissues, indicating that the unintended effects may be low. However, since there is a low permeability in other organs, it may not be a good candidate for drug repurposing. These findings are yet inconclusive; hence, further investigation is needed to verify the results of this investigation.