Title:Synthesis, Structure Activity Relationship (SAR), and Biological Activities of Benzylideneacetophenones Derivatives
Volume: 14
Issue: 3
Author(s): Alka N. Choudhary, Arun Kumar and Vijay Juyal
Affiliation:
Keywords:
Antioxidants, antiulcer, benzylideneacetophenone, inflammation.
Abstract: Background: Oxygen has double-edge properties as it is essential for life, but can also provoke
oxidative stress by protein & lipid per oxidation. The persistent oxidative stress and excess LPO
induce several inflammatory mediators such as prostaglandins and leuckotrienes by activating enzymes
cyclooxygenase and lipoxygenase. The per oxidation can be blocked by free radical scavengers as antiinflammatory
agents. Most of the anti-inflammatory agents, which inhibit the above mentioned enzymes, are associated
with side effects such as ulceration and bleeding in gastrointestinal tract; so the attention is focused on benzylideneacetophenones
having antinflammatory, antioxidant and gastric protectant activities by virtue of free radical scavengers. A systematic
analysis of the structural features responsible for biological activities and a possible mode of their actions were
proposed to be evaluated by synthesizing a set of compounds, screening them for anti-inflammatory, antioxidant and antiulcer
activity.
Methods: The benzylideneacetophenones derivatives were synthesized employing the Claisen-Schmidt condensation. The
structure of the compounds were established by IR, 1H NMR and mass spectral analysis. All the compounds were evaluated
for their anti-inflammatory (carrageenan-induced rat paw edema assay), antioxidant (inhibition of lipid peroxidation)
and antiulcer activity (indomethacin-induced gastric damage). Possible correlation between observed biological activities
and substituents at different positions on rings was also studied.
Results: The data revealed that compounds 1e, 1m and 1l showed equivalent activity to indomethacin (reference drug) at
the fourth hour at dose of 100 mg/kg. Among the tested compounds 1m & 1l exhibited the highest lipid per oxidation inhibitory
activity (IC50 2.38µg/ml, 3.08 µg/ml) followed by 1i, 1h, 1e. In addition, all compounds at the tested dose level
(100mg/kg, p.o.) exhibited varying degree of activity against ulceration induced by indomethacin. The compounds 1m, 1l,
1e, and 1i showed excellent activity (71-75%), whereas compounds 1d, 1h and 1j exhibited good to moderate (60-69%)
activity. SAR analysis revealed that presence of electron donating groups on p- position of both rings A and B seems to
enhance anti-inflammatory, antioxidant and antiulcer activity.
Conclusion: The compound 1m (4-amino-4’-ethoxychalcone) and 1l (4-amino-4’-methoxychalcone) have equivalent antiinflammatory
activity in comparison with the reference drug. Moreover, the same compounds also obtained promising antioxidant
and antiulcer activities. Thus, I m could be explored further for development of potent anti inflammatory agent.
