Mannich bases derivatives of 2-Phenyl-5-Benzimidazole sulfonic acid; Synthesis, Characterization, Computational studies and Biological evaluation

Abstract A new series of N-Mannich bases of 2-Phenyl-5-benzimidazole sulfonic acid have been synthesized through amino methylation reaction with secondary amines. The two moieties were held together through a methylene bridge, which comes from formaldehyde (Formalin Solution 37%) used in the reaction. Chemical structures of the newly synthesized compounds have been confirmed using FT-IR, 1HNMR and 13CNMR. Different in vitro assays including Anti-oxidant, Enzyme inhibition, Anti-microbial and Cytotoxicity assay were performed to evaluate the biological potential with reference to the standard drug. Among the synthesized library, compound 3a shows maximum alpha-glucosidase inhibition with an IC50 value of 66.66 μg/ml, compound 3d was found most toxic with LC50 value of 10.17 μg/ml. ADME evaluation studies were performed with the help of Molinspiration online software. Docking calculations were also performed. Given the importance of the nucleus involved, the synthesized compound might find extensive medicinal applications as reported in the literature.摘要：本研究通过二级胺参与的氨基甲基化反应，合成了一系列2-苯基-5-苯并咪唑磺酸的新型N-曼尼希碱。反应所使用的甲醛（37%福尔马林溶液）提供了连接两个结构单元的亚甲基桥。采用傅里叶变换红外光谱（FT-IR）、氢核磁共振波谱（¹HNMR）及碳核磁共振波谱（¹³CNMR）对新合成化合物的化学结构进行了确证。以标准药物为参照，通过体外抗氧化、酶抑制、抗菌及细胞毒性等多种实验，评估了所合成化合物的生物学活性潜力。在所构建的化合物库中，化合物3a对α-葡萄糖苷酶的抑制活性最强，其半数抑制浓度（IC₅₀）为66.66 μg/ml；化合物3d的细胞毒性最高，半数致死浓度（LC₅₀）为10.17 μg/ml。借助Molinspiration在线软件完成了吸收、分布、代谢、排泄（ADME）性质评价研究，同时开展了分子对接计算。鉴于所涉及母核结构的重要性，如已有文献报道所示，本研究合成的化合物有望获得广泛的医药应用。