Design, synthesis, in vitro evaluation, molecular docking and ADME properties studies of hybrid bis-coumarin with thiadiazole as a new inhibitor of Urease

Alomari M 1 , Taha M 2 , Imran S 3 , Jamil W 4 , Selvaraj M 5 , Uddin N 6 Show all authors , Rahim F 7

Affiliations 

  • 1 Department of Stem Cell Biology, Institute for Research and Medical Consultations, Imam Abdulrahman Bin Faisal University, P.O. Box. 1982, Dammam 31441, Saudi Arabia
  • 2 Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia. Electronic address: mtaha@uod.edu.sa
  • 3 Atta-ur-Rahman Institute for Natural Products Discovery (AuRIns), Universiti Teknologi MARA Cawangan Selangor Kampus Puncak Alam, 42300 Bandar Puncak Alam, Selangor D. E., Malaysia
  • 4 Institute of Advance Research Studies in Chemical Sciences, University of Sindh Jamshoro, Hyderabad 76080, Pakistan
  • 5 Monash University School of Chemical Engineering, 47500 Selangor Alam Campus, Bandar Subway 42300, Malaysia
  • 6 Department of Chemistry, University of Karachi, Karachi 75270, Pakistan
  • 7 Department of Chemistry, Hazara University, Mansehra 21300, Khyber Pakhtunkhwa, Pakistan
Bioorg Chem, 2019 11;92:103235.
PMID: 31494327 DOI: 10.1016/j.bioorg.2019.103235

Abstract

Hybrid bis-coumarin derivatives 1-18 were synthesized and evaluated for their in vitro urease inhibitory potential. All compounds showed outstanding urease inhibitory potential with IC50 value (The half maximal inhibitory concentration) ranging in between 0.12 SD 0.01 and 38.04 SD 0.63 µM (SD standard deviation). When compared with the standard thiourea (IC50 = 21.40 ± 0.21 µM). Among these derivatives, compounds 7 (IC50 = 0.29 ± 0.01), 9 (IC50 = 2.4 ± 0.05), 10 (IC50 = 2.25 ± 0.05) and 16 (IC50 = 0.12 ± 0.01) are better inhibitors of the urease compared with thiourea (IC50 = 21.40 ± 0.21 µM). To find structure-activity relationship molecular docking as well as absorption, distribution, metabolism, and excretion (ADME) studies were also performed. Various spectroscopic techniques like 1H NMR, 13C NMR, and EI-MS were used for characterization of all synthesized analogs. All compounds were tested for cytotoxicity and found non-toxic.

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

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