Quantitative Structure-Activity Relationship (QSAR) Study of Some DNA-Intercalating Anticancer Drugs

摘要

Small molecular anticancer drugs bind reversibly to DNA and are used in chemotherapy. The experimental measurements of the inhibition activity of drugs are difficult, expensive, and time-consuming. So, quantitative structure-activity/property relationship method (QSAR) is adopted where the dependency of drug binding affinity with their structural features is exploited. To explore whether molecular descriptors can explain their DNA-binding affinity and toxicity, 23 antitumor molecules, which are being used clinically as drugs, are analyzed by rigorous statistical calculations. The 50% cancer cell growth inhibition constant (IC50) for any particular cancer cell line is obtained from the NCI/NIH database. Molecular descriptors (geometrical, physicochemical, and quantum chemical) are calculated for the molecules. A mathematical model is built to predict DNA-drug-binding constant and growth inhibitory concentration by multiple regression which can be useful for rational drug design.