In silico drug repurposing: An antifungal drug, itraconazole, repurposed as an anticancer agent using molecular docking

Abstract

Introduction: In recent years, increased cancer incidences and death rates due to it, have turned cancer to be a major problem worldwide. Approximately more than 7 million people globally die from cancer. Among the various types of cancer, breast cancer is the most prevalent type of malignant neoplasms among the women. Owing to the increasing triple-negative breast cancer (TNBC) cases per year, there is a high demand for the development of new potential drugs within a short period. Objectives: The objectives of this study were to overcome the traditional drug discovery challenges and to deal with hazardous diseases with potential drugs within a less time using molecular docking as the most important bioinformatics tool used for computer-aided drug designing (CADD). Materials and Methods: For designing drug against TNBC, Smoothened (SMO) protein involved in the hedgehog pathway is selected, and an antifungal agent itraconazole is taken as a drug, which already exists but is repurposed using bioinformatics tools such as National Centre for Biotechnology Information (NCBI), Protein Data Bank (PDB), KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway database, Computed Atlas of Surface Topography of proteins (CASTp)/metaPocket, PubChem, DrugBank, MarvinView, Discovery Studio, and AutoDock tool. Similarly, the effect of the drug was tested in vitro on TNBC cell line (MDA-MB-231) using 3-(4, 5-dimethythiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Results: It was observed that cell viability decreased when different drug concentrations were used against TNBC cell lines in vitro as compared with the control sample, which lacked the drug sample. The cell viability observed was 100% in the control sample, 91% in 15.625 µM drug concentration, 71.5% in 31.25 µM drug concentration, 65.25% in 62.5 µM drug concentration, 54.75% in 125 µM drug concentration, 40.5% in 250 µM drug concentration, and 43% in 500 µM drug concentration. Conclusion: Repurposing of drug with the help of molecular docking is an effective method of drug development, which reduces time and cost of development of drug, and as it has already been approved, its safety measures are already known to make them safe to use. It is concluded that itraconazole shows an inhibitory effect on SMO, and thus it can be used as an anticancer agent.