Department of Chemistry, College of Science, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi Arabia.
Pharmacognosy and Pharmaceutical Chemistry Department, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi Arabia.
Int J Mol Sci. 2021 Jan 25;22(3):1162. doi: 10.3390/ijms22031162.
A library of novel imidazole-1,2,3-triazole hybrids were designed and synthesized based on the hybrid pharmacophore approach. Therefore, copper(I)catalyzed click reaction of thiopropargylated-imidazole 2 with several organoazides yielded two sets of imidazole-1,2,3-triazole hybrids carrying different un/functionalized alkyl/aryl side chains and . After full spectroscopic characterization using different spectral techniques (IR, H, C NMR) and elemental analyses, the resulted adducts were screened for their anticancer activity against four cancer cell lines (Caco-2, HCT-116, HeLa, and MCF-7) by the MTT assay and showed significant activity. In-silico molecular docking study was also investigated on one of the prominent cancer target receptors, i.e., glycogen synthase kinase-3β (GSK-3β), revealing a good binding interaction with our potent compound, and was in agreement with the in vitro cytotoxic results. In addition, the ADMET profile was assessed for these novel derivatives to get an insight on their pharmacokinetic/dynamic attributes. Finally, this research design and synthesis offered click chemistry products with interesting biological motifs mainly 1,2,3 triazoles linked to phenyl imidazole as promising candidates for further investigation as anticancer drugs.
基于杂合药效团方法，设计并合成了一系列新型咪唑-1,2,3-三唑杂合物库。因此，通过铜（I）催化硫代丙炔基-咪唑 2 与几种有机叠氮化物的点击反应，得到了两组带有不同未/功能化的烷基/芳基侧链的咪唑-1,2,3-三唑杂合物和。使用不同的光谱技术（IR、H、C NMR）和元素分析对得到的加合物进行了全光谱表征后，通过 MTT 法对它们针对四种癌细胞系（Caco-2、HCT-116、HeLa 和 MCF-7）的抗癌活性进行了筛选，并显示出显著的活性。还对其中一个突出的癌症靶受体，即糖原合酶激酶-3β（GSK-3β）进行了计算机分子对接研究，揭示了与我们的有效化合物的良好结合相互作用，并且与体外细胞毒性结果一致。此外，还评估了这些新型衍生物的 ADMET 概况，以深入了解它们的药代动力学/动态特性。最后，这项研究设计和合成提供了具有有趣生物基序的点击化学产物，主要是 1,2,3-三唑连接到苯基咪唑上，作为进一步研究作为抗癌药物的有希望的候选物。
