Department of Chemistry, University of Malakand, P.O. Box 18800, Dir Lower, Khyber Pakhtunkhwa, Pakistan.
Department of Chemistry, University of Malakand, P.O. Box 18800, Dir Lower, Khyber Pakhtunkhwa, Pakistan.
Bioorg Chem. 2018 Oct;80:472-479. doi: 10.1016/j.bioorg.2018.06.032. Epub 2018 Jun 30.
A new series of N-acylhydrazone derivatives of 2-mercaptobenzimidazole (2-MBI) has been synthesized through S-alkylation with 1-bromotetradecane and N-alkylation with ethyl-2-chloroacetate. The resulting ester was synthetically modified through hydrazine hydrate to acyl hydrazide which was condensed with aromatic aldehydes to afford the title N-acylhydrazones (4-17). Chemical structures of the newly synthesized compounds have been confirmed through mass, FT-IR and HNMR techniques. In vitro free radical scavenging and α-glucosidase inhibition activities of the compounds were investigated with reference to the standard ascorbic acid and acarbose, respectively. Amongst the target compounds, 13 showed the highest inhibition in DPPH scavenging assay (IC = 131.50 µM) and α-glucosidase inhibition potential (IC = 352 µg/ml). We extended our investigations to explore the mechanism of enzyme inhibition and conducted docking analysis by using Molecular Operating Environment (MOE 2016.08). A homology model for α-glucosidase was constructed and validated using Ramachandran plot. Docking studies were also carried out on human intestinal α-glucosidases. In view of the importance of the nucleus involved, the synthesized compounds might find extensive medicinal applications as reported in the literature.
通过与 1-溴十四烷的 S-烷基化和与氯乙酸乙酯的 N-烷基化，合成了一系列新的 2-巯基苯并咪唑（2-MBI）N-酰基腙衍生物。所得酯通过肼水合进一步合成修饰为酰基酰肼，然后与芳香醛缩合得到标题 N-酰基腙（4-17）。通过质谱、FT-IR 和 HNMR 技术确认了新合成化合物的化学结构。参考标准抗坏血酸和阿卡波糖，分别研究了化合物的体外自由基清除和α-葡萄糖苷酶抑制活性。在目标化合物中，13 号化合物在 DPPH 清除测定（IC = 131.50 µM）和 α-葡萄糖苷酶抑制潜力（IC = 352 µg/ml）方面表现出最高的抑制活性。我们进一步扩展了研究，探索了酶抑制的机制，并使用分子操作环境（MOE 2016.08）进行了对接分析。使用 Ramachandran 图构建和验证了α-葡萄糖苷酶的同源模型。还对人肠α-葡萄糖苷酶进行了对接研究。鉴于涉及的核的重要性，正如文献报道的那样，合成的化合物可能会作为广泛的药物应用。
