Department of Chemistry, Hazara University, Mansehra 21120, Pakistan.
Department of Chemistry, School of Natural Sciences (SNS), National University of Science and Technology (NUST), H-12, Islamabad 46000, Pakistan.
Molecules. 2022 Oct 29;27(21):7368. doi: 10.3390/molecules27217368.
The current study was conducted to obtain hybrid analogues of indole-based thiadiazole derivatives (-) in which a number of reaction steps were involved. To examine their biological activity in the presence of the reference drug Donepezil (0.21 ± 0.12 and 0.30 ± 0.32 M, respectively), the inhibitory potentials of AChE and BuChE were determined for these compounds. Different substituted derivatives showing a varied range of inhibitory profiles, when compared to the reference drug, analogue was shown to have potent activity, with IC50 values for AchE 0.15 ± 0.050 M and BuChE 0.20 ± 0.10, respectively, while other substituted compounds displayed good to moderate potentials. Varied spectroscopic techniques including H, CNMR and HREI-MS were used to identify the basic skeleton of these compounds. Furthermore, all analogues have a known structure-activity relationship (SAR), and molecular docking investigations have verified the binding interactions of molecule to the active site of enzymes.
本研究旨在获得基于吲哚的噻二唑衍生物的混合类似物（-），其中涉及多个反应步骤。为了在参考药物多奈哌齐（分别为 0.21 ± 0.12 和 0.30 ± 0.32 M）存在的情况下检查它们的生物活性，我们测定了这些化合物对 AChE 和 BuChE 的抑制潜力。与参考药物相比，不同取代的衍生物显示出不同范围的抑制谱，类似物表现出很强的活性，AChE 的 IC50 值为 0.15 ± 0.050 M，BuChE 的 IC50 值为 0.20 ± 0.10，而其他取代的化合物则显示出良好到中等的潜力。我们使用了多种光谱技术，包括 H、CNMR 和 HREI-MS，以鉴定这些化合物的基本骨架。此外，所有类似物都具有已知的构效关系（SAR），分子对接研究验证了分子与酶活性位点的结合相互作用。
