Alzheimer's dementia (AD), the most prevalent neurodegenerative disorder adversely affecting elderly citizens worldwide, is an incurable disorder with no effective medication found till date. Taking into account the seriousness of this issue, imidazopyridine-based benzothiazole-oxadiazole hybrid derivatives were synthesized as anti-Alzheimer's agents. The efficacy of these scaffolds was compared with the standard Donepezil (IC = 14.47 ± 1.20 μM for AChE and 19.90 ± 2.40 μM for BuChE). All the novel scaffolds exhibited biological activity covering a range of IC = 6.70 ± 1.65 μM and 41.65 ± 7.20 μM for AChE and 6.40 ± 1.80 μM for AChE and 44.65 ± 7.40 μM for BuChE. Analog 6p having IC = 6.70 ± 1.65 μM for AChE and 6.40 ± 1.80 μM for BuChE was found as the lead candidate of the series with maximum inhibition due to presence of small sized and highly electronegative fluoro moieties, inhibiting the enzymes through effective hydrogen bonds. These effective interactions were also studied in molecular docking investigations of the lead compounds. Furthermore, ADME analysis conducted in this study assisted the drug likeness of the potent analogs. Synthetic and structural confirmation of the hybrid derivatives was achieved through C NMR, H NMR and HREI-MS.

中文翻译：

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一种有前途的乙酰胆碱酯酶和丁酰胆碱酯酶抑制剂：含咪唑并吡啶杂化衍生物的苯并噻唑基恶二唑的体外酶促和计算机分子对接研究

阿尔茨海默氏痴呆（AD）是一种最常见的神经退行性疾病，对全世界老年人产生不利影响，是一种无法治愈的疾病，迄今为止尚未发现有效的药物。考虑到这个问题的严重性，合成了基于咪唑并吡啶的苯并噻唑-恶二唑杂化衍生物作为抗阿尔茨海默病药物。将这些支架的功效与标准多奈哌齐进行比较（AChE 的 IC = 14.47 ± 1.20 μM，BuChE 的 IC = 19.90 ± 2.40 μM）。所有新型支架均表现出生物活性，AChE 的 IC 值范围为 6.70 ± 1.65 μM 和 41.65 ± 7.20 μM，AChE 的范围为 6.40 ± 1.80 μM，BuChE 的范围为 44.65 ± 7.40 μM。类似物 6p 对于 AChE 的 IC = 6.70 ± 1.65 μM，对于 BuChE 的 IC = 6.40 ± 1.80 μM，被发现是该系列的主要候选者，由于存在小尺寸和高电负性的氟部分，通过有效的氢键抑制酶，因此具有最大的抑制作用。这些有效的相互作用也在先导化合物的分子对接研究中进行了研究。此外，本研究中进行的 ADME 分析有助于确定有效类似物的药物相似性。通过 C NMR、H NMR 和 HREI-MS 实现了杂化衍生物的合成和结构确认。