Department of Biochemistry and Microbiology, North South University, Bashundhara,, Dhaka, 1217, Bangladesh.
Biological and Environmental Sensing Research Unit, King Abdullah Institute for Nanotechnology, King Saud University, 11451, Riyadh, Saudi Arabia.
Sci Rep. 2024 Jun 8;14(1):13221. doi: 10.1038/s41598-024-63237-y.
In exploring nature's potential in addressing diabetes-related conditions, this study investigates the therapeutic capabilities of 3-formyl chromone derivatives. Utilizing in silico methodologies, we focus on 6-substituted 3-formyl chromone derivatives (1-16) to assess their therapeutic potential in treating diabetes. The research examined the formyl group at the chromone's C-3 position. ADMET, biological activities, were conducted along with B3LYP calculations using 3 different basis sets. The analogues were analyzed based on their parent structure obtained from PubChem. The HOMO-LUMO gap confirmed the bioactive nature of the derivatives, NBO analysis was performed to understand the charge transfer. PASS prediction revealed that 3-formyl chromone derivatives are potent aldehyde oxidase inhibitors, insulin inhibitors, HIF1A expression inhibitors, and histidine kinase. Molecular docking studies indicated that the compounds had a strong binding affinity with proteins, including CAD, BHK, IDE, HIF-α, p53, COX, and Mpro of SARS-CoV2. 6-isopropyl-3-formyl chromone (4) displayed the highest affinity for IDE, with a binding energy of - 8.5 kcal mol. This result outperformed the affinity of the reference standard dapagliflozin (- 7.9 kcal mol) as well as two other compounds that target human IDE, namely vitexin (- 8.3 kcal mol) and myricetin (- 8.4 kcal mol). MD simulations were revealed RMSD value between 0.2 and 0.5 nm, indicating the strength of the protein-ligand complex at the active site.
在探索大自然在解决与糖尿病相关的疾病方面的潜力时，本研究调查了 3-甲酰基色酮衍生物的治疗能力。我们利用计算方法，专注于 6-取代的 3-甲酰基色酮衍生物（1-16），以评估它们在治疗糖尿病方面的治疗潜力。研究考察了色酮 C-3 位上的甲酰基。同时进行了 ADMET 和生物活性测试，以及使用 3 种不同基组的 B3LYP 计算。根据从 PubChem 获得的母体结构对类似物进行了分析。HOMO-LUMO 能隙证实了衍生物的生物活性，NBO 分析用于理解电荷转移。PASS 预测表明，3-甲酰基色酮衍生物是潜在的醛氧化酶抑制剂、胰岛素抑制剂、HIF1A 表达抑制剂和组氨酸激酶抑制剂。分子对接研究表明，这些化合物与包括 CAD、BHK、IDE、HIF-α、p53、COX 和 SARS-CoV2 的 Mpro 在内的蛋白质具有很强的结合亲和力。6-异丙基-3-甲酰基色酮（4）对 IDE 的亲和力最高，结合能为-8.5 kcal/mol。这一结果优于参考标准达格列净（-7.9 kcal/mol）以及另外两种靶向人 IDE 的化合物，即牡荆素（-8.3 kcal/mol）和杨梅素（-8.4 kcal/mol）的亲和力。MD 模拟显示 RMSD 值在 0.2 到 0.5nm 之间，表明蛋白质-配体复合物在活性位点的强度。
