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Medicinal Chemistry Research

, Volume 24, Issue 3, pp 1196–1209 | Cite as

Metronidazole derivatives as a new class of antiparasitic agents: synthesis, prediction of biological activity, and molecular properties

  • Dua’ Y. Alawadi
  • Haythem A. Saadeh
  • Hargobinder Kaur
  • Kapil Goyal
  • Rakesh Sehgal
  • Taibi Ben Hadda
  • Naser A. ElSawy
  • Mohammad S. MubarakEmail author
Original Research

Abstract

Series of new metronidazole urea and thiourea derivatives have been prepared in good yields through reactions of 2-(2-methyl-5-nitroimidazolyl) ethylamine hydrochloride with various cyanates and isothiocyanates. Similarly, metronidazole hydroxybenzoic acid derivatives were synthesized by reacting 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl-4-methylbenzene sulfonate (4) with m- and p-hydroxybenzoic acids. Structures of the newly prepared compounds were confirmed through different spectroscopic methods such as 1H-NMR, 13C-NMR, mass spectrometry and also by elemental analyses. The antigiardial and antitrichomonal activities of the prepared compounds were evaluated in vitro. Compounds 3a, 3b, 3c, 3d, 3f, 3g, 3j, 3l, 3m, and 6b exhibited remarkable antigiardial activity with IC50 values ranging from 5.2 to 7.5 µg/mL and were found to be more active than metronidazole which has an IC50 of 8.0 µg/mL. Similarly, several of the tested compounds showed significant antitrichomonal activity with IC50 values ranging from 4.95 to 6.80 µg/mL compared with the standard drug, metronidazole which has an IC50 of 8.0 µg/mL. Compound 6b was the most potent among the prepared compounds and was about 1.6 times more active than metronidazole. In addition, the newly synthesized products were subjected to Petra/Osiris/Molinspiration (POM) analyses to get insights on the degree of their toxicity.

Keywords

Metronidazole (1-ethyl-2-methyl-5-nitro-1H-imidazole) derivatives Urea and thiourea derivatives Antigiardial and antitrichomonal activity Petra/Osiris/Molinspiration (POM) analyses 

Notes

Acknowledgments

The authors express their gratitude to the ACTELION, the Biopharmaceutical Company of Swiss, for the molecular properties calculations.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Dua’ Y. Alawadi
    • 1
  • Haythem A. Saadeh
    • 1
  • Hargobinder Kaur
    • 2
  • Kapil Goyal
    • 2
  • Rakesh Sehgal
    • 2
  • Taibi Ben Hadda
    • 3
  • Naser A. ElSawy
    • 4
  • Mohammad S. Mubarak
    • 1
    Email author
  1. 1.Department of ChemistryThe University of JordanAmmanJordan
  2. 2.Department of Medical ParasitologyPostgraduate Institute of Medical Education and ResearchChandigarhIndia
  3. 3.Laboratoire de Chimie des Matériaux (LCM), Faculté des SciencesUniversité Mohammed PremierOujdaMorocco
  4. 4.Department of Anatomy and Embryology, Faculty of MedicineZagazig UniversityZagazigEgypt

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