H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 31441, Dammam, Saudi Arabia.
Int J Biol Macromol. 2022 Jun 30;211:653-668. doi: 10.1016/j.ijbiomac.2022.05.040. Epub 2022 May 11.
Variety of 2-aryl quinoxaline derivatives 1-23 were synthesized in good yields, by reacting 1,2-phenylenediamine with varyingly substituted phenacyl bromides in the presence of pyridine catalyst. All molecules 1-23 were characterized by spectroscopic techniques and evaluated for their diverse biological potential against α-amylase (α-AMY), α-glucosidase (α-GLU), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) enzymes. Synthetic derivatives possess enhanced inhibitory potential against all enzymes at nanomolar concentrations. In particular, compound 14 was found much superior with IC = 294.35, 198.21, 17.04, and 21.46 nM against α-AMY, α-GLU, AChE, and BChE, respectively, as compared to standard inhibitors. Furthermore, selected potent compounds, including 3, 4, 8, 14, 15, 17, and 18, were subjected to molecular docking studies to decipher the binding energies and interactions of ligands (synthetic molecules) with all four target enzymes.
合成了多种 2-芳基喹喔啉衍生物 1-23，通过 1,2-苯二胺与不同取代的苯乙酮溴化物在吡啶催化剂存在下反应得到。所有的分子 1-23 都通过光谱技术进行了表征，并评估了它们对α-淀粉酶（α-AMY）、α-葡萄糖苷酶（α-GLU）、乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）的多种生物潜力。合成衍生物在纳摩尔浓度下对所有酶都具有增强的抑制潜力。特别是化合物 14 对 α-AMY、α-GLU、AChE 和 BChE 的 IC 50 值分别为 294.35、198.21、17.04 和 21.46 nM，与标准抑制剂相比，其抑制活性明显更高。此外，选择了一些有效化合物，包括 3、4、8、14、15、17 和 18，进行了分子对接研究，以解析配体（合成分子）与所有四种靶酶的结合能和相互作用。
