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

by Selleckchem | Aug 15 2023

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.

Comments:

The study you described focuses on the synthesis and evaluation of a new series of hybrid hydrazone and phthalimide compounds as potential analgesic agents. The researchers designed and synthesized these compounds by reacting specific aldehydes with 2-aminophthalimide. They then assessed the analgesic, cyclooxygenase inhibitory, and cytostatic activities of the prepared compounds.

The results of the study indicated that all the tested ligands exhibited significant analgesic activity. Specifically, compounds 3i and 3h were identified as the most potent ligands in the formalin and writhing tests, respectively. Additionally, compounds 3g, 3j, and 3l displayed high selectivity towards cyclooxygenase-2 (COX-2), which is an enzyme involved in inflammation. Among the tested compounds, ligand 3e was found to be the most potent COX inhibitor, with a COX-2 selectivity ratio of 0.79. The researchers observed that the presence of electron-withdrawing moieties with hydrogen bonding ability at the meta position had a significant impact on the selectivity of the ligands. Compounds 3g, 3l, and 3k demonstrated high COX-2 selectivity, with compound 3k being the most potent among them.

Furthermore, the study evaluated the cytostatic activity of selected ligands. Compounds 3e, 3f, 3h, 3k, and 3m exhibited good analgesic and COX inhibitory activity while demonstrating lower toxicity compared to the reference drug.

In conclusion, the synthesized hybrid hydrazone and phthalimide compounds demonstrated significant analgesic activity, selective COX-2 inhibition, and favorable cytostatic properties. These compounds exhibited a high therapeutic index, which is a valuable advantage indicating their potential as analgesic agents.