Affiliations 

  • 1 Department of Chemistry, Baghdad-ul-Jadeed Campus, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
  • 2 Department of Chemistry, Government College University Lahore, Lahore, Pakistan
  • 3 Institute for Biological Interfaces (IBG-1), Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany
  • 4 School of Pharmacy, Monash University Malaysia, Subang Jaya, Malaysia
Arch Pharm (Weinheim), 2019 Dec;352(12):e1900095.
PMID: 31544284 DOI: 10.1002/ardp.201900095

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, 1 H-NMR (nuclear magnetic resonance), 13 C-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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.