Hybrid Analogues of Hydrazone and Phthalimide: Design, Synthesis, In vivo, In vitro, and In silico Evaluation as Analgesic Agents
- Авторлар: 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
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Мекемелер:
- Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences,, Tehran Islamic Azad Medical Sciences University,
- Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Tehran Islamic Azad Medical Sciences University,
- Department of Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences
- Department of Toxicology, School of Pharmacy,, Shahid Beheshti University of Medical Sciences
- Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences,, Tehran Islamic Azad Medical Sciences University,
- Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences,, Tehran Islamic Azad Medical Sciences University
- Department of Toxicology, School of Pharmacy,, Shahid Beheshti University of Medical Sciences,
- Department of Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences,
- Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences, Tehran Islamic Azad Medical Sciences University,
- Шығарылым: Том 20, № 5 (2024)
- Беттер: 685-696
- Бөлім: Chemistry
- URL: https://rjpbr.com/1573-4099/article/view/644264
- DOI: https://doi.org/10.2174/1573409919666230517121726
- ID: 644264
Дәйексөз келтіру
Толық мәтін
Аннотация
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.
Негізгі сөздер
Авторлар туралы
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,
Хат алмасуға жауапты Автор.
Email: info@benthamscience.net
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