我们目前正在进行一个级联的尝试来开发新的高效分子，这涉及到设计一系列的咪唑衍生物，并通过Debus-Radziszewski多组分合成反应原理合成两套2,4,5-三取代咪唑化合物(4a-4d)和1,2,4,5-四取代咪唑化合物(6a-6d)。所得化合物的结构经过了1H/13C NMR、FT-IR、元素分析、纯度以及通过HPLC进行的保留时间分析进行了确认。基于分子对接研究中的结合亲和力，我们合成了不同的咪唑衍生物，其中6c化合物显示出更高的抗增生活性，通过增加细胞凋亡的速率，与其他化合物的体外预测结果相一致。化合物4d的结构和结晶性质经过了单晶XRD分析进行了确认。我们对合成的分子在三阴性乳腺癌细胞系(MDA-MB-231)、胰腺癌细胞系(MIA PaCa-2)和口腔鳞状细胞癌细胞系(H357)中进行了体外抗癌性能筛选实验，结果表明所有化合物在不同时间点的浓度依赖性抑制了细胞增殖。化合物4b和6d对金黄色葡萄球菌菌株具有一定的抑制作用，而只有化合物4d对白色念珠菌菌株具有适度的抑制作用，最小抑菌浓度为12.5μg/mL。分子对接研究揭示出合成的化合物与参与肿瘤发生的MELK靶点之间的良好相互作用和高结合特性。我们进一步对领先化合物6c进行了详细的分子动力学研究，以确定配体-酶复合物的稳定性。版权所有 © 2023. 由Elsevier B.V.出版。

Our cascading attempt to develop new potent molecules now involves designing a series of imidazole derivatives and synthesizing two sets of 2,4,5- tri-substituted (4a-4d) and 1,2,4,5-tetra-substituted (6a-6d) imidazole by the principle of Debus-Radziszewski multicomponent synthesis reaction. The structures of the obtained compounds were confirmed by 1H/13C NMR, FT-IR, elemental analysis, purity and the retention time was analyzed by HPLC. Based upon the binding affinity in the molecular docking studies, we have synthesized different imidazole derivatives from which compound 6c have been found to show more anti-proliferative activity by inducing apoptosis at a higher rate than the other compounds corroborating the in-silico prediction. The structure and crystallinity of compound 4d have been confirmed by single XRD analysis. The synthesized molecules were screened for their in vitro anti-cancer properties in triple negative breast cancer cell line (MDA-MB-231), pancreatic cancer cell lines (MIA PaCa-2) and oral squamous cell carcinoma cell line (H357) and results indicated that all the compounds inhibited the cell proliferation in a concentration-dependent manner at different time points. The compounds 4b and 6d were found to be effective against the S. aureus bacterial strain whereas only compound 4d fairly inhibited the fungal strain of T. rubrum with a MIC 12.5 μg/mL. Molecular docking study reveals good interaction of the synthesized compounds with known target MELK involved in oncogenesis having high binding profiles. The lead compound 6c was further analyzed by the detailed molecular dynamics study to establish the stability of the ligand-enzyme complex.Copyright © 2023. Published by Elsevier B.V.