Synthesis of benzimidazole derivatives as new α-Glucosidase inhibitors

Synthesis of 4-(5,6-dimethyl-1 H-benzo[d]imidazole-2-yl)benzohydrazide Schiff bases (1-26) was accomplished by three-step procedure as shown in the scheme below. Equimolar solution of 4-formylbenzoic acid methyl ester, 4,5-dimethyl-O-phenylenediamine and sodium meta bisulfite in dimethylformamide (DMF) was refluxed for six hours to give out the arylester substituted benzimidazole [1]. The benzohydrazide of benzimidazole was formed by refluxing arylester of benzimidazole with methanolic hydrazine hydrate. The synthesis of new benzimidazole benzohydrazide Schiff bases (1-26) was accomplished by reacting different aldehydes with benzimidazole benzohydrazide in n-butanol in the presence of catalytic amount of acetic acid and were further evaluated for their α-glucosidase inhibitory activity. Compounds 1-26 exhibited varying degrees of yeast α-glucosidase inhibitory activity with IC₅₀ values between 8.40 ± 0.76 – 179.71 ± 1.11µM when compared with standard acarbose. In this assay, seven compounds that showed highest inhibitory effects than the rest of benzimidazole series were identified. All the synthesized compounds were characterized by different spectroscopic methods adequately such as 1D NMR, IR and HREIMS.

Acknowledgements: The authors would like to acknowledge the Ministry of Higher Education (MOHE) and Universiti Teknologi MARA for the financial support under RAGS grant 600-RMI/RAGS/5/3/(2/2012).

Keywords: Synthesis, benzimidazole, α-Glucosidase inhibitory activity.

References:

[1] Taha M, Ismail NH, Jamil W, Rashwan H, Kashif SM, Sain AA, Adenan MI, Anouar EH, Ali M, Rahim F, Khan KM. Synthesis of novel derivatives of 4-methylbenzimidazole and evaluation of their biological activities. Eur J Med Chem 2014; 84: 731 – 738