Application of a Validated QSTR Model for Repurposing COX-2 Inhibitor Coumarin Derivatives as Potential Antitumor Agents
Objective: The first aim of the study was to develop a validated linear model to predict antitumor activity. Subsequently, applicability of the model for repurposing these cyclooxygenase-2 inhibitors as antitumor compounds to abridge drug development process.
Methods: We performed a quantitative structure-toxicity relationship (QSTR) study on a set of coumarin derivatives using a large set of molecular descriptors. A linear model predicting growth inhibition on leukemia CCRF cell lines was developed and consequently validated internally and externally. Accordingly, the model was applied on a set of 143 cyclooxygenase-2 inhibitor coumarin derivatives to explore their antitumor activity.
Results: The results indicated that the developed QSAR model would be useful for estimating inhibitory activity of coumarin derivatives on leukemia cell lines. Electronegativity was found to be a prominent property of the molecules in describing antitumor activity. The applicability domain of the developed model highlighted the potential antitumor compounds.
Conclusion: The promising results revealed that applied integrated in silico approach for repurposing by combining both the biological activity similarity and the molecular similarity via the computational method could be efficiently used to screen potential antitumor compounds among cyclooxygenase-2 inhibitors.
Document Type: Research Article
Publication date: May 1, 2019
This article was made available online on June 26, 2019 as a Fast Track article with title: "Application of a Validated QSAR Model for Repurposing COX-2 Inhibitor Coumarin Derivatives as Potential Antitumor Agents".