Network pharmacology and molecular docking study-based approach to explore mechanism of benzimidazole-based anthelmintics for the treatment of lung cancer

AbstractEmerging studies have reported the potential anticancer activity of benzimidazole-based anthelmintics (BBA) against lung cancer (LC). However, mechanism underlying the anticancer activity of BBA is unclear. Therefore, in the current study, network pharmacology and molecular docking-based approach were used to explore the potential molecular mechanism for the treatment of LC. The potential targets for BBA were obtained from multiple databases including SwissTargetPrediction, Drug Bank, Therapeutic Target Database, and Comparative Toxicogenomics Database while LC targets were collected from DisGeNet gene discovery platform, Integrated Genomic Database of NSCLC, Catalogue of Somatic Mutations in Cancer and Online Mendelian Inheritance in Man database. Protein-protein interaction (PPI) diagram of common targets was constructed using STRING online platform. Topological analysis was performed using Cytoscape and gene enrichment analysis was conducted using FunRich software. Highest degree targets were then confirmed using molecular docking and molecular dynamics simulations. The BBA were prioritized according to their S scores, with ricobendazole ranking highest followed by flubendazole, fenbendazole, mebendazole, triclabendazole, albendazole, oxibendazole, parbendazole, thiabendazole and oxfendazole. The potential targets of BBA identified using topological analysis and molecular docking were found to be CCND1 (cyclin D1), EGFR (Epidermal Growth Factor Receptor), ERBB2 (Erb-B2 Receptor Tyrosine Kinase 2/CD340), PTGS2 (Prostaglandin-endoperoxide synthase 2), and SRC (Proto-oncogene tyrosine-protein kinase). Furthermore, molecular dynamics confirmed that CCND1 and EGFR are the potential targets of ricobendazole for the treatment of LC. BBA can be further explored as a therapeutic strategy for the treatment of lung cancer under in vitro and in vivo studies.Communicated by Ramaswamy H. SarmaKeywords: Benzimidazole-based anthelminticslung cancermolecular dockingmolecular dynamicsnetwork pharmacology AcknowledgementsAuthors gratefully acknowledge Bioinformatics Resources and Applications Facility (BRAF) of the Center for Development of Advanced Computing (CDAC, Pune), India for providing adequate computational facility in the Biogene cluster.Disclosure statementNo potential conflict of interest was reported by the authors.Author’s contributionAG: Conceptualization, Data curation, Formal analysis, methodology, project administration, writing-original draftIAK: Computational Conceptualization, formal analysis, validationSK: Methodology, formal analysisAB: Data curation, review manuscriptR: MethodologyN: Scientific inputs and conceptualisationMAK: Scientific inputs, Conceptualization, formal analysis and supervisionAdditional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.