Rauf Abdur, Alam Waqas, Khan Momin, Darwish Hany W, Daglia Maria, Elhenawy Ahmed A, Khan Haroon
Department of Pharmacy, Abdul Wali Khan University, Mardan - Pakistan.
Department of Chemistry, Abdul Wali Khan University, Mardan - Pakistan.
Drug Target Insights. 2025 Mar 10;19:11-17. doi: 10.33393/dti.2025.3271. eCollection 2025 Jan-Dec.
Adequate hyperglycemic control is still a huge challenge with the clinically used therapeutics. New, more effective anti-diabetic agents are on the top list of drug discovery projects.
This article deals with the in vitro anti-diabetic potential of 2, 3 dichloroIndolinone (C1) and 2, 6-dichloroIndolinone (C2) on α-glucosidase and α-amylase followed by in silico analysis.
Both compounds, C-1 and C-2, caused significant inhibition of α-glucosidase at various test concentrations with IC of 35.266 μM and 38. 379 μM, respectively. Similarly, compounds C-1 and C-2 elicited significant anti-α-amylase action with IC values of 42.449 μM and 46.708 μM, respectively. The molecular docking investigation regarding the α-glucosidase and α-amylase binding site was implemented to attain better comprehension with respect to the pattern in which binding mechanics occur between the C1 and C2 molecules and the active sites, which illustrated a higher binding efficacy in appraisal with reference inhibitor and acarbose. The interactions between the active compounds C1 and C2 with the active site residues were mainly polar bonds, hydrogen bonding, π-π, and π-H interactions, which contributed to a strong alignment with the enzyme backbone. Similarly, effective binding is frequently indicated by a strong and stable hydrogen-bonding pattern, which is suggested by the minimal fluctuation in MM-PBSA values.
In short, this study will contribute to providing these compounds with an improved anti-diabetic profile and decreased toxicity.
使用临床治疗药物实现充分的高血糖控制仍然是一项巨大挑战。新型、更有效的抗糖尿病药物位居药物研发项目的前列。
本文研究了2,3-二氯吲哚酮（C1）和2,6-二氯吲哚酮（C2）对α-葡萄糖苷酶和α-淀粉酶的体外抗糖尿病潜力，并进行了计算机模拟分析。
化合物C-1和C-2在不同测试浓度下均对α-葡萄糖苷酶有显著抑制作用，IC50分别为35.266 μM和38.379 μM。同样，化合物C-1和C-2对α-淀粉酶也有显著的抑制作用，IC50值分别为42.449 μM和46.708 μM。对α-葡萄糖苷酶和α-淀粉酶结合位点进行了分子对接研究，以便更好地理解C1和C2分子与活性位点之间的结合机制，结果表明与参考抑制剂和阿卡波糖相比，它们具有更高的结合效率。活性化合物C1和C2与活性位点残基之间的相互作用主要是极性键、氢键、π-π和π-H相互作用，这有助于与酶骨架形成强排列。同样，有效的结合通常由强烈而稳定的氢键模式表示，MM-PBSA值的最小波动表明了这一点。
简而言之，本研究将有助于改善这些化合物的抗糖尿病特性并降低毒性。
