Department of Pharmaceutical Chemistry, Faculty of Clinical Pharmacy, Al Baha University, Al Baha 65779, Saudi Arabia.
Int J Mol Sci. 2023 Feb 15;24(4):3882. doi: 10.3390/ijms24043882.
Hexaconazole is widely used as a fungicide for agricultural purposes. However, the endocrine-disrupting potential of hexaconazole is still under investigation. In addition, an experimental study found that hexaconazole may disrupt the normal synthesis of steroidal hormones. The potency of hexaconazole to bind with sex hormone-binding globulin (SHBG), a plasma carrier protein that binds androgens and oestrogens, is unknown. In this study, we evaluated the efficacy of hexaconazole to bind with SHBG by molecular interaction, a molecular dynamics method. In addition, principal component analysis was performed to understand the dynamical behaviour of hexaconazole with SHBG in comparison with dihydrotestosterone and aminoglutethimide. The binding scores of hexaconazole, dihydrotestosterone, and aminoglutethimide with SHBG were found to be -7.12 kcal/mol, -11.41 kcal/mol, and -6.84 kcal/mol, respectively. With respect to stable molecular interaction, hexaconazole showed similar molecular dynamics patterns of root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), and hydrogen bonding. The solvent surface area (SASA) and principal component analysis (PCA) of hexaconazole exhibit similar patterns in comparison with dihydrotestosterone and aminoglutethimide. These results show that hexaconazole has a stable molecular interaction with SHBG, which may acquire the active site of the native ligand, resulting in significant endocrine disruption during agricultural work.
六氯环己烷被广泛用作农业杀菌剂。然而，六氯环己烷的内分泌干扰潜力仍在研究中。此外，一项实验研究发现，六氯环己烷可能会干扰甾体激素的正常合成。六氯环己烷与性激素结合球蛋白（SHBG）的结合能力，SHBG 是一种结合雄激素和雌激素的血浆载体蛋白，其结合能力尚不清楚。在这项研究中，我们通过分子相互作用，即分子动力学方法，评估了六氯环己烷与 SHBG 结合的效果。此外，还进行了主成分分析，以了解六氯环己烷与 SHBG 的动力学行为与二氢睾酮和氨鲁米特的比较。六氯环己烷、二氢睾酮和氨鲁米特与 SHBG 的结合评分分别为-7.12 kcal/mol、-11.41 kcal/mol 和-6.84 kcal/mol。就稳定的分子相互作用而言，六氯环己烷表现出与 RMSD（均方根偏差）、RMSF（均方根波动）、Rg（回转半径）和氢键相似的分子动力学模式。溶剂表面积（SASA）和主成分分析（PCA）的六氯环己烷与二氢睾酮和氨鲁米特的表现模式相似。这些结果表明，六氯环己烷与 SHBG 具有稳定的分子相互作用，可能获得了天然配体的活性位点，从而在农业工作中导致显著的内分泌干扰。
