Benzimidazole derivatives as new α-glucosidase inhibitors and in silico studies

Nik Khairunissa Nik Abdullah Zawawi; Muhammad Taha; Norizan Ahmat; Abdul Wadood; Nor Hadiani Ismail; Fazal Rahim; Syed Sikander Azam; Noraishah Abdullah

doi:10.1016/j.bioorg.2015.11.006

Benzimidazole derivatives as new α-glucosidase inhibitors and in silico studies

Bioorg Chem. 2016 Feb:64:29-36. doi: 10.1016/j.bioorg.2015.11.006. Epub 2015 Nov 23.

Authors

Nik Khairunissa Nik Abdullah Zawawi¹, Muhammad Taha², Norizan Ahmat³, Abdul Wadood⁴, Nor Hadiani Ismail¹, Fazal Rahim⁵, Syed Sikander Azam⁶, Noraishah Abdullah⁷

Affiliations

¹ Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D. E., Malaysia; Faculty of Applied Science, UiTM Shah Alam, 40450 Shah Alam, Selangor D.E., Malaysia.
² Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D. E., Malaysia; Faculty of Applied Science, UiTM Shah Alam, 40450 Shah Alam, Selangor D.E., Malaysia. Electronic address: taha_hej@yahoo.com.
³ Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D. E., Malaysia; Faculty of Applied Science, UiTM Shah Alam, 40450 Shah Alam, Selangor D.E., Malaysia. Electronic address: noriz118@salam.uitm.edu.my.
⁴ Department of Chemistry, Abdul Wali Khan University Mardan, Khyber Pakhtunkhwa, Pakistan.
⁵ Department of Chemistry, Hazara University Mansehra, 21300 Khyber Pakhtunkhwa, Pakistan.
⁶ Department of Bioinformatics, Quaide-e-Azam University, Islamabad, Pakistan.
⁷ Faculty of Applied Science, UiTM Shah Alam, 40450 Shah Alam, Selangor D.E., Malaysia.

PMID: 26637946
DOI: 10.1016/j.bioorg.2015.11.006

Abstract

Newly synthesized benzimidazole hydrazone derivatives 1-26 were 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 and 179.71 ± 1.11 μM 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. We further evaluated the interaction of the active compounds with enzyme with the help of docking studies.

Keywords: Benzimidazole; Hydrazone; In silico studies; α-Glucosidase activity.

MeSH terms

Acarbose / chemistry
Benzimidazoles / chemical synthesis
Benzimidazoles / chemistry*
Glycoside Hydrolase Inhibitors / chemical synthesis
Glycoside Hydrolase Inhibitors / chemistry*
Hydrazones / chemical synthesis
Hydrazones / chemistry*
Molecular Docking Simulation
Saccharomyces cerevisiae / enzymology*
Stereoisomerism
Structure-Activity Relationship
alpha-Glucosidases / chemistry*

Substances

Benzimidazoles
Glycoside Hydrolase Inhibitors
Hydrazones
alpha-Glucosidases
Acarbose