Background: “Angiogenesis”, a major oncogenic signaling pathway, has been termed to be the most fascinating area of cancer therapy. Viewing this, the molecular chaperone Hsp90 has surfaced as a potential molecular target due to being vitally engrossed in sustaining stability, integrity, and functions of crucial proteins involved in multiple signaling pathways of tumor progression and metastasis.

Objective: The study set sights on virtual screening (molecular docking and PreADMET study), MD simulation, and metabolism study of compounds from Crucifereae family along with the intensive structure-activity relationship studies in search of potent lead targeting HSP90.

Methods: All the chemical structures were drawn using ChemDraw and converted into suitable 3D-structures. The target protein, HSP90 was retrieved from RCSB PDB. All the compounds of Crucifereae family and analogs were subjected to Lipinski’s rule of five and ADMET prediction using Molinspiration and PreADMET software respectively. The screened compounds were further exposed to MD simulation and metabolism studies.

Conclusion: The docking results showed the promising inhibitory potential of Ana51 against Hsp90 with the binding energy of -11.32 kcal/mol as compared to its parent compound ‘spirobrassinin’ and a known inhibitor ‘Ganetespib’ exhibiting binding energy of -7.57 kcal/mol and -9.83 kcal/mol respectively. Optimization, flexibility prediction, and ascertaining the stability of Hsp90 in complex with the ligands were done by means of Molecular Dynamics (MD) simulations for 50 ns. The Hsp90-Ana51 complex exhibited stability with an RMSD value of 0.15 nm and Rg value to be 1.62 nm. The investigation further extends towards the SOM analysis of Ana51 to forecast the probable toxic and non-toxic in vivo metabolites via in silico tools (SMARTCyp, Xenosite Web, and PASS online server).

Results: Ana 51 came out to be metabolically stable withstanding phase I metabolism and producing non-toxic metabolites compared to the parent compound and the standard drug. Obtained results propose Ana51 as a novel anti-Hsp90 lead compound with exceptional antiangiogenic capability.

背景：“血管生成”是一种主要的致癌信号通路，被称为癌症治疗中最引人入胜的领域。鉴于此，分子伴侣 Hsp90 已成为潜在的分子靶标，因为它非常专注于维持参与肿瘤进展和转移的多个信号通路的关键蛋白质的稳定性、完整性和功能。

目的：该研究着眼于十字花科化合物的虚拟筛选（分子对接和 PreADMET 研究）、MD 模拟和代谢研究，以及深入的构效关系研究，以寻找针对 HSP90 的有效铅。

方法：所有化学结构均使用 ChemDraw 绘制并转换为合适的 3D 结构。从 RCSB PDB 中检索到目标蛋白 HSP90。所有十字花科化合物及其类似物分别使用 Molinspiration 和 PreADMET 软件进行 Lipinski 五法则和 ADMET 预测。筛选的化合物进一步暴露于 MD 模拟和代谢研究。

结论：对接结果表明 Ana51 对 Hsp90 的抑制潜力为 -11.32 kcal/mol，与其母体化合物“spirobrassinin”和已知抑制剂“Ganetespib”相比，结合能为 -7.57 kcal/mol 和分别为-9.83 kcal/mol。通过 50 ns 的分子动力学 (MD) 模拟进行优化、灵活性预测和确定 Hsp90 与配体复合物的稳定性。Hsp90-Ana51 复合物表现出稳定性，RMSD 值为 0.15 nm，Rg 值为 1.62 nm。调查进一步扩展到 Ana51 的 SOM 分析，以通过计算机工具（SMARTCyp、Xenosite Web 和 PASS 在线服务器）预测可能的有毒和无毒体内代谢物。

结果：与母体化合物和标准药物相比，Ana 51 代谢稳定，可承受 I 期代谢并产生无毒代谢物。获得的结果表明 Ana51 是一种具有特殊抗血管生成能力的新型抗 Hsp90 先导化合物。