Comparative In-Silico Evaluation of Common Over-the-Counter Drugs as Potential Binders of Human Carbonic Anhydrase IX Using AutoDock Vina

Abstract

Carbonic Anhydrase IX (CA-IX) is a hypoxia-induced, tumor-associated zinc metalloenzyme that plays a critical role in regulating pH homeostasis in cancer cells and is considered a promising molecular target in anticancer research [1-3]. Drug repurposing using computational approaches provides a cost-effective strategy for identifying novel interactions between approved drugs and therapeutic targets [4]. In the present study, a comparative molecular docking analysis was performed to evaluate the binding potential of five commonly used over-the-counter (OTC) drugs—paracetamol, ibuprofen, aspirin, caffeine, and cetirizine—against human Carbonic Anhydrase IX using AutoDock Vina [5]. The crystal structure of CA-IX (PDB ID: 3IAI) was prepared by removing co-crystallized ligands while retaining the catalytically essential Zn²⁺ ion. All ligands were docked using a focused grid centered on the Zn²⁺-containing active site. Docking results revealed that cetirizine exhibited the strongest binding affinity (–7.6 kcal/mol), followed by ibuprofen (–7.2 kcal/mol), paracetamol (–6.6 kcal/mol), aspirin (–6.5 kcal/mol), and caffeine (–5.9 kcal/mol). The study highlights differential binding patterns among OTC drugs and provides preliminary computational evidence supporting their potential interaction with CA-IX, warranting further experimental investigation.