QSAR Modeling of Camptothecin Derivatives Targeting Topoisomerase I: StructuralInsights for Anticancer Drug Design

Introduction:: This study investigates the quantitative structure–activity relationship (QSAR) of camptothecin derivatives to determine how variations in their structures affect the activity of these derivatives on Topoisomerase I (Top I), a crucial enzyme involved in DNA replication in cancer cells. Methods:: A total of 55 camptothecin derivatives were divided into training and test sets, with biological activity (IC50) as the dependent variable. A Partial Least Squares (PLS) Regression model was developed using the calculated molecular descriptors to predict the IC50 values. objective: - Results:: The R² and Q² values were 0.99852 and 0.249, respectively. QSAR results indicate that molar refractivity, hydrophilicity, molecular weight, and the ether group count highly contribute to the expected activity of camptothecin (CPT) derivatives on Top I. Conclusion:: This study presents a computational approach to better understand how the structure of camptothecin derivatives affects their activity against Topoisomerase I, which could inform the future design of more effective anticancer drugs. result: The R2 and Q2 squared were 0.99852 and 0.249, respectively. QSAR results indicate that molar refractivity, hydrophilicity, molecular weight and ether group count highly contribute to expected activity of CPT derivatives on Top 1. other: -