Hybrid Analogues of Hydrazone and Phthalimide: Design, Synthesis, In vivo, In vitro, and In silico Evaluation as Analgesic Agents

  • Authors: Shokri S.1, Ayazi H.2, Tamjid M.3, Ghoreishi F.4, Shokri M.5, Badakhshannouri S.6, Naderi N.7, Daraei B.8, Mousavi Z.9, Davood A.2
  • Affiliations:
    1. Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences,, Tehran Islamic Azad Medical Sciences University,
    2. Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Tehran Islamic Azad Medical Sciences University,
    3. Department of Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences
    4. Department of Toxicology, School of Pharmacy,, Shahid Beheshti University of Medical Sciences
    5. Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences,, Tehran Islamic Azad Medical Sciences University,
    6. Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences,, Tehran Islamic Azad Medical Sciences University
    7. Department of Toxicology, School of Pharmacy,, Shahid Beheshti University of Medical Sciences,
    8. Department of Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences,
    9. Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences, Tehran Islamic Azad Medical Sciences University,
  • Issue: Vol 20, No 5 (2024)
  • Pages: 685-696
  • Section: Chemistry
  • URL: https://rjpbr.com/1573-4099/article/view/644264
  • DOI: https://doi.org/10.2174/1573409919666230517121726
  • ID: 644264

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Full Text

Abstract

Background:Based on the anti-inflammatory and analgesic activity of hydrazone and phthalimide, a new series of hybrid hydrazone and phthalimide pharmacophores was prepared and evaluated as analgesic agents.

Methods:The designed ligands were synthesized by reaction of the appropriate aldehydes and 2- aminophthalimide. Analgesic, cyclooxygenase inhibitory, and cytostatic activity of prepared compounds were measured.

Results:All the tested ligands demonstrated significant analgesic activity. Moreover, compounds 3i and 3h were the most potent ligands in the formalin and writhing tests, respectively. Compounds 3g, 3j, and 3l were the most COX-2 selective ligands and ligand 3e was the most potent COX inhibitor with a 0.79 of COX-2 selectivity ratio. The presence of electron-withdrawing moieties with hydrogen bonding ability at the meta position was found to affect the selectivity efficiently, in which compounds 3g, 3l, and 3k showed high COX-2 selectivity, and compound 3k was the most potent one. The cytostatic activity of selected ligands demonstrated that compounds 3e, 3f, 3h, 3k, and 3m showed good analgesic and COX inhibitory activity and were less toxic than the reference drug.

Conclusion:High therapeutic index of these ligands is one of the valuable advantages of these compounds.

About the authors

Shahla Shokri

Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences,, Tehran Islamic Azad Medical Sciences University,

Email: info@benthamscience.net

Hoda Ayazi

Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Tehran Islamic Azad Medical Sciences University,

Email: info@benthamscience.net

Mohsen Tamjid

Department of Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences

Email: info@benthamscience.net

Fatemeh Ghoreishi

Department of Toxicology, School of Pharmacy,, Shahid Beheshti University of Medical Sciences

Email: info@benthamscience.net

Mahsa Shokri

Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences,, Tehran Islamic Azad Medical Sciences University,

Email: info@benthamscience.net

Sogol Badakhshannouri

Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences,, Tehran Islamic Azad Medical Sciences University

Email: info@benthamscience.net

Nima Naderi

Department of Toxicology, School of Pharmacy,, Shahid Beheshti University of Medical Sciences,

Email: info@benthamscience.net

Bahram Daraei

Department of Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences,

Email: info@benthamscience.net

Zahra Mousavi

Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences, Tehran Islamic Azad Medical Sciences University,

Email: info@benthamscience.net

Asghar Davood

Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Tehran Islamic Azad Medical Sciences University,

Author for correspondence.
Email: info@benthamscience.net

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