Background: Inflammation is a biological rejoinder of vascular tissues against destructive
agents e.g. irritants, damaged cell or pathogens. During inflammation, respiratory burst occurs by activated
phagocytes which help to destroy invading pathogens. Phagocytic cells such as neutrophils and
macrophages are one of the major sources of reactive oxygen species (ROS) and nitric oxide (NO).
Normally, the redox environment is maintained by various antioxidant defense systems, however, these
reactive oxygen species may be destructive and can lead to various pathological conditions.
Methods: Benzophenone esters and sulfonates (1-18) were synthesized through one pot synthesis by
reacting 4-hydroxy benzophenone either different benzoyl chloride or sulfonyl chloride. These synthetic
compounds were evaluated for their in vitro immunosuppressive potential on two parameters of
innate immune response including inhibition of intracellular reactive oxygen species (ROS) and nitric
oxide (NO). ROS were induced in polymorphonuclear leukocytes (PMNs) isolated from human whole
blood by serum opsonized zymosan stimulation, whereas NO were produced in J774.2 cells by
lipopolysachharides (LPS) stimulation. Moreover, cytotoxicity of compounds was also determined using
NIH-3T3 fibroblast cells (ATCC, Manassas, USA) was evaluated by using the standard MTT colorimetric
Results: All compounds inhibited the production of ROS at various extent among which compounds
2, 5, 6, 8, 10, 13 and 16 were found to be the potent inhibitors of ROS with IC50 values ranging between
(1.0 - 2.2 µg/mL) as compared to ibuprofen (IC50 = 2.5 ± 0.6 µg/mL) as the standard drug. Compounds
2, 7, 11, 13, 14 and 18 showed good inhibition of NO production with % inhibition values
ranging between (63.6% - 76.7%) at concentration of 25 µg/mL as compared to NG-monomethyl-Larginine
(L-NMMA 65.6 ± 1.1 µg/mL) as the standard. All other derivatives showed moderate to low
level of inhibition on both tested parameters. Cytotoxicity activity also showed nontoxicity of synthetic
compounds. Structures of all the synthetic compounds were confirmed through 1H-NMR, 13C-NMR,
EI-MS and HREI-MS spectroscopic techniques.
Conclusion: Compounds 2 and 13 were found to be good dual antiinflammatory (ROS and NO) agent.
However, compounds 5, 6, 8, 10 and 16 were found to be selectively active for ROS inhibitory studies.
Compounds 7, 11, 14 and 18 were discriminatory active at NO inhibition assay. These initial findings
of antiinflammatory activity concluded that these compounds might have the potential to develop a
novel non-steroidal antiinflammatory drugs (NSAIDs), non-acidic antiinflammatory agent. Most active
compounds 2, 5-8, 10, 13, 14 and 16 showed nontoxicity of synthetic compounds.