New Bis-Pyrazolones as Potential Leads for ROS Inhibition; Environment Friendly Green Synthesis, Structural Characterization, and In Vitro Studies

摘要

Background: Pyrazolones have identified as significant antioxidant agents and manymarketed and clinically prescribed NSAIDs have pyrazolone ring as main scaffold.Method: Keeping in consideration the antioxidant potential of pyrazolone scaffold, new bispyrazolones3-30 were synthesized by a green and enviroment friendly reaction route, in whichtwo equivalents of 1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-ol were treated with one equivalentof benzaldehyde derivatives without any catalyst. All compounds were structurally characterziedby 1H-NMR and FAB analysis. 13C-NMR of selected compounds was also recorded. All compoundsgave satisfactory elemental analyses and found in good agreement with calculated values.Results: Synthetic bis-pyrazolones 3-30 were evaluated for their oxidative burst inhibitory effectof zymosan stimulated whole blood phagocytes by using luminol enhanced chemilluminescencetechnique. All molecules demonstrated the potent ROS inhibition activity in the range of IC50 = 1.2± 0.1-48.8 ± 3.9 μM as compared to the standard ibuprofen (IC50 = 54.2 ± 9.2 μM). The purity ofactive compounds was checked by HPLC.Conclusion: This study has identified a number of non-acidic lead molecules for future researchon ROS inhibitors.