Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut Campus, P.O. Box 13-5053, Chouran, Beirut 1102 2801, Lebanon.
Department of Computer Science and Mathematics, Lebanese American University, Beirut Campus, P.O. Box 13-5053, Chouran, Beirut 1102 2801, Lebanon.
Biomolecules. 2024 Jul 17;14(7):860. doi: 10.3390/biom14070860.
One of the most challenging issues scientists face is finding a suitable non-invasive treatment for cancer, as it is widespread around the world. The efficacy of phytochemicals that target oncogenic pathways appears to be quite promising and has gained attention over the past few years. We investigated the effect of docking phytochemicals isolated from the rhizomes of the Cimicifuga foetida plant on different domains of the IκB kinase alpha (IKK1/alpha) protein. The Cimicifugoside H-2 phytochemical registered a high docking score on the activation loop of IKK1/alpha amongst the other phytochemicals compared to the positive control. The interaction of the protein with Cimicifugoside H-2 was mostly stabilized by hydrogen bonds and hydrophobic interactions. A dynamic simulation was then performed with the Cimicifugoside H-2 phytochemical on the activation loop of IKK1/alpha, revealing that Cimicifugoside H-2 is a possible inhibitor of this protein. The pharmacokinetic properties of the drug were also examined to assess the safety of administering the drug. Therefore, in this in silico study, we discovered that the Cimicifugoside H-2 phytochemical inhibits the actively mutated conformation of IKK1/alpha, potentially suppressing the nuclear factor kappa light chain enhancer of activated B cells (NF-κB) pathway.
科学家面临的最具挑战性的问题之一是寻找一种合适的非侵入性癌症治疗方法，因为癌症在全球范围内广泛存在。近年来，靶向致癌途径的植物化学物质的疗效似乎很有前景，引起了人们的关注。我们研究了从升麻属植物根茎中分离出的植物化学物质对接不同结构域的 IκB 激酶 alpha（IKK1/alpha）蛋白的效果。与阳性对照相比，Cimicifugoside H-2 植物化学物质在 IKK1/alpha 的激活环上的对接得分高于其他植物化学物质。该蛋白与 Cimicifugoside H-2 的相互作用主要通过氢键和疏水相互作用稳定。然后对 Cimicifugoside H-2 植物化学物质在 IKK1/alpha 的激活环上进行了动态模拟，结果表明 Cimicifugoside H-2 可能是该蛋白的抑制剂。还检查了药物的药代动力学特性，以评估给药的安全性。因此，在这项计算机研究中，我们发现 Cimicifugoside H-2 植物化学物质抑制 IKK1/alpha 的活跃突变构象，可能抑制核因子 kappa 轻链增强子的激活 B 细胞（NF-κB）途径。
