Department of Biotechnology, KLE Technological University, Hubballi 580031, India.
Department of Mechanical Engineering, College of Engineering, King Khalid University, Abha 61421, Saudi Arabia.
Molecules. 2023 Mar 7;28(6):2430. doi: 10.3390/molecules28062430.
Finding structurally similar compounds in compound databases is highly efficient and is widely used in present-day drug discovery methodology. The most-trusted and -followed similarity indexing method is Tanimoto similarity indexing. Epigenetic proteins like histone deacetylases (HDACs) inhibitors are traditionally used to target cancer, but have only been investigated very recently for their possible effectiveness against rheumatoid arthritis (RA). The synthetic drugs that have been identified and used for the inhibition of HDACs include SAHA, which is being used to inhibit the activity of HDACs of different classes. SAHA was chosen as a compound of high importance as it is reported to inhibit the activity of many HDAC types. Similarity searching using the UNPD database as a reference identified aglaithioduline from the compound as having a ~70% similarity of molecular fingerprints with SAHA, based on the Tanimoto indexing method using ChemmineR. Aglaithioduline is abundantly present in the shell and fruits of . In silico studies with aglaithioduline were carried out against the HDAC8 protein target and showed a binding affinity of -8.5 kcal mol. The complex was further subjected to molecular dynamics simulation using Gromacs. The RMSD, RMSF, compactness and SASA plots of the target with aglaithioduline, in comparison with the co-crystallized ligand (SAHA) system, showed a very stable configuration. The results of the study are supportive of the usage of and in Indian traditional medicine for the treatment of pain-related ailments similar to RA. Our study therefore calls for further investigation of and for their potential use against RA by targeting epigenetic changes, using in vivo and in vitro studies.
在化合物数据库中寻找结构相似的化合物是非常高效的，在当今的药物发现方法中得到了广泛应用。最受信任和遵循的相似性索引方法是 Tanimoto 相似性索引。表观遗传蛋白，如组蛋白去乙酰化酶（HDAC）抑制剂，传统上用于靶向癌症，但最近才开始研究它们对类风湿关节炎（RA）的可能有效性。已经鉴定和用于抑制 HDAC 的合成药物包括 SAHA，它被用于抑制不同类别 HDAC 的活性。SAHA 被选为一种重要的化合物，因为据报道它可以抑制多种 HDAC 类型的活性。使用 UNPD 数据库作为参考进行相似性搜索，根据 ChemmineR 使用 Tanimoto 索引方法，从化合物中鉴定出 aglaithioduline 与 SAHA 的分子指纹相似性约为 70%。aglaithioduline 在 的壳和果实中大量存在。对 aglaithioduline 进行了针对 HDAC8 蛋白靶标的计算机研究，显示出 -8.5 kcal mol 的结合亲和力。进一步使用 Gromacs 对复合物进行了分子动力学模拟。与共晶配体（SAHA）系统相比，靶标与 aglaithioduline 的 RMSD、RMSF、紧凑性和 SASA 图显示出非常稳定的构型。研究结果支持印度传统医学中使用 和 治疗类似于 RA 的与疼痛相关的疾病。因此，我们的研究呼吁进一步研究 和 ，通过针对表观遗传变化，使用体内和体外研究，将其潜在用于治疗 RA。
