Design, Synthesis, Characterization, QSAR, Docking, Anti-inflammatory and Analgesic Evaluation of Some New Phthalazinediones

Author(s): Yousery E. Sherif, Ryan Alansari, Moustafa A. Gouda*.

Journal Name: Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

Volume 17 , Issue 1 , 2018

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Graphical Abstract:


Background: phthalazine derivatives were reported to possess anticonvulsant , cardiotonic , antibacterial, analgesic , anti-inflammatory, and anti-microbial activity. In the current study, we applied the QSAR for prediction of newly phthalazinediones incorporating thioamide moiety aiming to reach a more potent anti-inflammatory and Analgesic agent.

Methods: Phthalazinediones 10-15 have been synthesized through condensation of dibenzobarallene 3 with thiosemicarbazides 4-8. One equation was predicted using quantitative structure activity relationship (QSAR) and regression analysis for the anti-inflammatory activity with a regression correlation (R) close to unity. The docking studies were performed to investigate the biological trends of the organic compounds (thiol form) against cyclooxygenas- 2 enzyme, which is a responsible inflammation mediator by using Molgro Virtual Docker (MVD) software. The anti-inflammatory activity and analgesic effect of the thioamides 10-15 were determined by collagen II-adjuvant induced paw edema test in rats.

Results: Compounds 10, 11, 12, and 14, exhibited promising anti-inflammatory activity. Furthermore, in the pain scoring, compounds 10, 11 and 12 were found to be more effective than piroxicam and the order of the analgesic effect of the investigated compounds is as followed 14 >12 > 10 > 11 > 15.

Conclusion: It is clear from the foregoing that the compound 14 is a promising compound if future pharmacological detailed studies. This is consistent with what has been predictable equation 1 in this study.

Keywords: Analgesic effect, anti-inflammatory activity, docking, phthalazine, QSAR, regression.

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Article Details

Year: 2018
Page: [3 - 15]
Pages: 13
DOI: 10.2174/1871523017666180413111321

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