Molecular interactions of vinclozolin metabolites with human estrogen receptors 1GWR-α and 1QKM and androgen receptor 2AM9-β: Implication for endocrine disruption

Background: Vinclozolin (VCZ) is a widely used antifungal agent with capability to enter into the human food chain. VCZ metabolizes into seven metabolites M1-M7. Several studies have shown its effects on reprotoxicity. However, there is limited information available on the interaction of VCZ metabolites with nuclear receptors. In silico studies aimed at identifying interaction of endocrine disruptor with nuclear receptors serve a prescreening framework in risk assessment. Methods: We studied interactive potential of VCZ and its metabolites with human estrogen (ER) and androgen receptor (AR) using molecular docking method. Binding potential of VCZ and its metabolites with estrogen receptors 1GWR-alpha, 1QKM and androgen receptor 2AM9-beta was checked by using Schrodinger Maestro 10.5. Estradiol (E2), a natural ligand of ER and AR was taken as a reference. Results: VCZ and its metabolites showed higher or similar binding efficiency on interaction with target proteins when compared with E2. VCZ and its metabolites also exhibited agonistic effect against 1GWR-alpha, 1QKM and 2AM9-beta with strong binding potential to them. Conclusion: Some VCZ metabolites such as M4 and M5 showed higher binding potencies with 1GWR-alpha, 1QKM and 2AM9-beta than E2. Toxicity data of VCZ is well endowed. However, endocrine disrupting potential of VCZ via nuclear receptor mediated pathway is less understood. This in silico study revealing that not only VCZ but its metabolites have potential to interact with 1GWR-alpha, 1QKM and 2AM9-beta offers a platform for further exploration of VCZ in this direction.