Alkhathami Ali G, Alshahrani Mohammad Y, Alshehri Saad Ali, Nasir Nazim, Wahab Shadma
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, P.O. Box 61413, Abha, 9088, Saudi Arabia.
Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha, 62529, Saudi Arabia.
Sci Rep. 2025 Jan 22;15(1):2871. doi: 10.1038/s41598-025-86289-0.
Previous research indicates that Transforming growth factor beta-3 (TGFβ3) expression levels correlate with breast cancer metastasis, and elevated TGFβ3 levels have been linked with poor overall survival in breast cancer patients. The study used computational methods to examine curcumin's effects on TGFβ3, a chemical with antiviral and anticancer characteristics. The curcumin has low Molecular Weight 368.130 (MW) and follows Lipinski Rule, Pfizer Rule, GSK Rule, Golden Triangle, BMS Rule, zero PAINS alert and Acute Toxicity Rule with zero alert. Any drug-like contender must follow these qualities. Through molecular docking analyses, curcumin displayed favourable binding affinities at the TGFβ3 binding pocket, forming key interactions such as hydrogen bonds with residues like ASP323, ARG325, VAL333, HIS334, PRO336, LYS337, GLY393, and ARG394. 500 ns molecular dynamic simulations examined docking interactions. Molecular dynamics (MD) simulations trajectories analysis, by calculating lower structural deviation, minimal residual fluctuations, structural compactness assessment by calculating radius of gyration, surface area calculation which interact with solvent, role of hydrogen bonding, and secondary structural analyses. Furthermore, principal component, Gibbs free energy landscape and MMPBSA analysis, signifying system stability. These data suggest curcumin may inhibit TGFβ3, providing a framework for developing new compounds targeting this protein.
先前的研究表明，转化生长因子β-3（TGFβ3）的表达水平与乳腺癌转移相关，并且TGFβ3水平升高与乳腺癌患者较差的总生存率有关。该研究使用计算方法来研究姜黄素对TGFβ3的影响，TGFβ3是一种具有抗病毒和抗癌特性的化学物质。姜黄素的分子量较低，为368.130（MW），符合Lipinski规则、辉瑞规则、葛兰素史克规则、金三角规则、百时美施贵宝规则，无PAINS警报且急性毒性规则为零警报。任何类药物候选物都必须具备这些特性。通过分子对接分析，姜黄素在TGFβ3结合口袋处显示出良好的结合亲和力，与ASP323、ARG325、VAL333、HIS334、PRO336、LYS337、GLY393和ARG394等残基形成氢键等关键相互作用。500纳秒的分子动力学模拟检验了对接相互作用。分子动力学（MD）模拟轨迹分析，通过计算较低的结构偏差、最小的残余波动、通过计算回转半径进行结构紧凑性评估、与溶剂相互作用的表面积计算、氢键的作用以及二级结构分析。此外，主成分分析、吉布斯自由能景观和MMPBSA分析，表明系统稳定性。这些数据表明姜黄素可能抑制TGFβ3，为开发针对该蛋白的新化合物提供了框架。
