A novel five-step synthetic route to 1,3,4-oxadiazole derivatives with potent α-glucosidase inhibitory potential and their in silico studies

Muhammad Iftikhar, Shahnawaz, Muhammad Saleem, Naheed Riaz, Aziz-ur-Rehman, Ishtiaq Ahmed, Jameel Rahman, Muhammad Ashraf, Muhammad S. Sharif, Shafi U. Khan, Thet T. Htar

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Abstract

A series of new N-aryl/aralkyl derivatives of 2-methyl-2-{5-(4-chlorophenyl)-1,3,4-oxadiazole-2ylthiol}acetamide were synthesized by successive conversions of 4-chlorobenzoic acid (a) into ethyl 4-chlorobenzoate (1), 4-chlorobenzoylhydrazide (2) and 5-(4-chlorophenyl)-1,3,4-oxadiazole-2-thiol (3), respectively. The required array of compounds (6a–n) was obtained by the reaction of 1,3,4-oxadiazole (3) with various electrophiles (5a–n) in the presence of DMF (N,N-dimethylformamide) and sodium hydroxide at room temperature. The structural determination of these compounds was done by infrared, 1H-NMR (nuclear magnetic resonance), 13C-NMR, electron ionization mass spectrometry, and high-resolution electron ionization mass spectrometry analyses. All compounds were evaluated for their α-glucosidase inhibitory potential. Compounds 6a, 6c–e, 6g, and 6i were found to be promising inhibitors of α-glucosidase with IC50 values of 81.72 ± 1.18, 52.73 ± 1.16, 62.62 ± 1.15, 56.34 ± 1.17, 86.35 ± 1.17, 52.63 ± 1.16 µM, respectively. Molecular modeling and ADME (absorption, distribution, metabolism, excretion) predictions supported the findings. The current synthesized library of compounds was achieved by utilizing very common raw materials in such a way that the synthesized compounds may prove to be promising drug leads.

Original languageEnglish
Article number1900095
Number of pages12
JournalArchiv der Pharmazie
Volume352
Issue number12
DOIs
Publication statusPublished - Dec 2019

Keywords

  • 4-chlorobenzoic acid
  • mercapto-N-aryl/aralkyl propionamide oxadiazoles
  • N-substituted-2-bromopropionamide
  • α-glucosidase inhibition

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