Abstract
The intracellular uptake concentration determines drug absorption, drug activity, and toxicity. Sesamol, sesamin, and sesamolin are promising bioactive components from Sesame indicum L. Their respective intracellular uptake pathway and cytotoxicity were evaluated using melanoma and non-cancerous cells. Quantitative structure-activity relationship (QSAR) models were built to identify the molecular features affecting drug uptake in cells. The respective intracellular uptake pathway for sesamol vs. sesamin and sesamolin was carrier-mediated vs. passive transport. Topological polar surface area (PSA) and 2D autocorrections increase the intracellular concentration (C/M ratio) of these compounds. Sesamol has the lowest C/M ratio compared to sesamin and sesamolin, but only sesamol inhibits the cell viability of melanoma and provides an inhibition concentration at 50% (IC_50) against melanoma cells. The slightly aqueous solubility of sesamin and sesamolin, therefore, limits testing of their cytotoxicity. In conclusion, sesamol has the potential to inhibit melanoma cell growth, but requires improvement of the C/M ratio to increase its physicochemical properties. Thus, in order to investigate the cytotoxicity of sesamin and sesamolin against melanoma cells a solubility enhancer is needed.
NSTL