Advances in In-Silico based Predictive In-Vivo Profiling of Novel Potent β-Glucuronidase Inhibitors

doi:10.2174/1568009619666190320102238

摘要

背景：肠道β-葡萄糖醛酸苷酶在大肠癌发生中具有重要意义。对该酶的特异性抑制有助于防止葡萄糖醛酸苷致癌物的免疫再激活，从而保护肠道免受ROS（活性氧化物种）介导的致癌作用。目标：基于计算机的进步为使用SwissADME和BOILED-Egg工具顺利进行药物设计和开发过程提供了广泛的研究。方法：在我们设计的案例研究中，我们使用SwissADME和BOILED-Egg预测性计算工具来评估我们最近在体外评估的新型β-葡糖醛酸苷酶抑制剂的理化，人药代动力学，药物相似性，药物化学性质和膜通透性特征。结果：在11种筛选的有效抑制剂中，化合物（8）相对于6个分子描述符表现出出色的生物利用度雷达，具有良好的（ADME）吸收，分布，代谢和排泄以及P-糖蛋白，CYP450同工酶和膜通透性特征。基于这些事实观察，可以预测化合物（8）可以有效地达到体内实验清除率，因此，在将来，它可以成为市场上用于治疗与过度表达甲状旁腺激素有关的各种疾病的药物。 β-葡萄糖醛酸苷酶，例如各种类型的癌症，尤其是激素依赖性癌症，例如（乳腺癌，前列腺癌和结肠癌）。此外，其他化合物（1-7和9-11）也显示出良好的预测药代动力学，药物化学，BBB和HIA膜通透性，并进行了轻微的铅优化，从而获得了改善的结果。结论：因此，基于计算机的研究被认为为合理的药物设计和开发方法提供了鲁棒性，从而避免了在药物开发阶段后期候选药物失败的可能性。这项研究的结果有效地揭示了有效的β-葡萄糖醛酸苷酶抑制剂的可能属性，以进行进一步的实验评估。

关键词: β-葡萄糖醛酸苷酶，结肠直肠癌变，SwissADME，水煮蛋，药代动力学，药物相似性，血脑屏障（BBB），人体肠道吸收（HIA）。

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DOI https://dx.doi.org/10.2174/1568009619666190320102238	Print ISSN 1568-0096
Publisher Name Bentham Science Publisher	Online ISSN 1873-5576

当代肿瘤药物靶点

新型强效β-葡萄糖醛酸酶抑制剂的体内预测分析研究进展

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当代肿瘤药物靶点

新型强效β-葡萄糖醛酸酶抑制剂的体内预测分析研究进展

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