Anticancer Potential of Fluoroquinazoline Analogues: An Integrated Computational and System Biology Study

Abstract

Cancer remains a major global health burden, with incidence rates rising globally. Although cancer can be cured if detected early and treated effectively, it is still a leading cause of death worldwide. Fluoroquinazoline scaffold, valued in medicine for their anticancer, anti-inflammatory, and antimicrobial properties. In the present study, we use a comprehensive approach by integrating network pharmacology, molecular docking techniques to explore the Fluoroquinazoline derivatives against cancer. Totally 149 compounds were retrieved from PubChem and they were subjected to physiochemical, pharmacokinetic, metabolic and toxicity profiles. The compounds which are having good pharmacokinetic and less toxic profile were selected for further studies. Network pharmacology and gene ontology enrichment were performed to identify the top targets involved in cancer progression. Molecular docking was performed using Mz-DOCK tool with Auto dock vina mode. A total of 14 compounds were finalized and network was constructed using Cytoscape. Top nine targets were identified, among them top two targets, namely, EGFR and PIK3CA, based on the degree centrality were selected. Molecular docking studies revealed that the compound (7-(cyclopropylmethoxy)-5-fluoro-2-(7-oxa-2- azaspiro [3.5] nonan-2-yl)-3H-quinazolin-4-one) showed good and highest binding energy and interaction profile. In conclusion, the results revealed that fluoroquinazoline derivatives can be the best analogues for the treatment of various cancers.