Gliomas are the most prevalent primary brain tumors in the central nervous system. ABC transporters have been identified as critical therapeutic targets in oncology, particularly in the context of overcoming chemoresistance. This study aims to investigate whether natural coumarins farnesiferol A, B and C (FFA, FFB and FFC) can inhibit the activity of drug transporters in glioma. Protein targets associated with low-grade glioma (LGG) and glioblastoma multiforme (GBM) were identified, along with potential molecular targets of verapamil—the standard inhibitor of ABC transporters. Interactome mapping was performed for the overlapping targets, followed by Gene Ontology enrichment analysis to elucidate their biological implications. The pharmacokinetics of FFA, FFB and FFC were evaluated, and these coumarins were subjected to molecular docking to assess their binding affinities for ABCB1 and ABCC1. Finally, molecular dynamics simulations assessed the conformational flexibility and binding stability of the FFA-ABCC1 complex. ABCB1 and ABCC1 were among the identified hub targets, and enrichment analyses confirmed their involvement in several biological processes. Computational predictions suggest that farnesiferols exhibit favorable pharmacokinetic profile, including high absorption, favorable distribution and low toxicity risks. Molecular docking demonstrated favorable interactions between FFA, FFB and FFC and the two ABC transporters, compared to the positive control verapamil. The binding affinity scores for FFA, FFB and FFC interacting with the active site of ABCB1 were − 7.3, − 7.0 and − 8.0 kcal/mol, respectively. For ABCC1, binding affinity scores were − 8.5, − 8.1 and − 8.1 kcal/mol for FFA, FFB and FFC, respectively. Molecular dynamics simulations also confirmed the flexibility and binding stability of the FFA-ABCC1 complex. In conclusion, present findings highlight the potential of farnesiferols as reversal agents for innovative strategies against glioma.

Keywords