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.