Affiliations 

  • 1 Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 31441, Dammam, Saudi Arabia. Electronic address: mtaha@iau.edu.sa
  • 2 Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D. E., Malaysia
  • 3 Department of Stem Cell Research, Institute for Research and Medical Consultations, Imam Abdulrahman Bin Faisal University, P. O. Box. 1982, Dammam 31441, Saudi Arabia
  • 4 Department of Chemistry, Hazara University, Mansehra 21120, Pakistan
  • 5 Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan
  • 6 Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 31441, Dammam, Saudi Arabia
  • 7 Department of Chemistry, University of Karachi, Karachi 75270, Pakistan
  • 8 Department of Computer Information Systems, College of Computer Science & Information Technology (CCSIT) Imam Abdulrahman Bin Faisal University P.O. Box 1982, Dammam 31441, Saudi Arabia
Bioorg. Med. Chem., 2019 07 15;27(14):3145-3155.
PMID: 31196753 DOI: 10.1016/j.bmc.2019.05.049

Abstract

A new series of oxadiazole with thiadiazole moiety (6-27) were synthesized, characterized by different spectroscopic techniques and evaluated for β-glucuronidase inhibitory potential. Sixteen analogs such as 6, 7, 8, 9, 10, 12, 13, 14, 17, 18, 20, 23, 24, 25, 26 and 27 showed IC50 values in the range of 0.96 ± 0.01 to 46.46 ± 1.10 μM, and hence were found to have excellent inhibitory potential in comparison to standard d-saccharic acid 1,4-lactone (IC50 = 48.4 ± 1.25 μM). Two analogs such as 16 and 19 showed moderate inhibitory potential while analogs 11, 15, 21 and 22 were found inactive. Our study identifies new series of potent β-glucuronidase inhibitors for further investigation. Structure activity relationships were established for all compounds which showed that the activity is varied due to different substituents on benzene ring. The interaction of the compounds with enzyme active site were confirmed with the help of docking studies, which reveals that the electron withdrawing group and hydroxy group make the molecules more favorable for enzyme inhibition.

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