title: Synthesis, Structure Activity Relationship (SAR), and Biological Activities of Benzylideneacetophenones Derivatives.
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, (1)H 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Medicinal Chemistry Research Laboratory, Department of Pharmaceutical Sciences, Shri Guru Ram Rai Institute of Technology & Science, Dehradun, Uttarakhand, India. alka_pharma@rediffmail.com.
authors.forename: Alka N
authors.initials: AN
authors.lastname: Choudhary
authors.forename: Arun
authors.initials: A
authors.lastname: Kumar
authors.forename: Vijay
authors.initials: V
authors.lastname: Juyal
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002351:Carrageenan; D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D007213:Indomethacin; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D013329:Structure-Activity Relationship
chemical_list: D000893:Anti-Inflammatory Agents; D000897:Anti-Ulcer Agents; D000975:Antioxidants; D047188:Chalcones; D002351:Carrageenan; D007213:Indomethacin