title: Triblock Conjugates: Identification of a Highly Potent Antiinflammatory Agent.
abstract: Rationally designed conjugates of chrysin, indole, and barbituric acid were synthesized and screened for their antiinflammatory activities through in vitro and in vivo experiments. Improved over the previously reported chrysin-indole-pyrazole conjugates and also in comparison to the chrysin, indole, and barbituric acid based COX-2 inhibitors, the new compounds have displayed significantly better IC50 for COX-2 and some of them also exhibited inhibition of 5-LOX enzyme. For one of the test compounds, IC50 for COX-2 and 5-LOX was 1 and 1.5 nM, respectively. Investigations of Swiss Albino mice through capsaicin induced paw lickings and dextran induced inflammation showed that these compounds possess appreciable analgesic and antiinflammatory activities. Ki, Ka, and ΔG for the enzyme-compound interaction were calculated and found to be in agreement with the biological data. The experimental results were supported by the molecular docking studies of the compounds in the active site of COX-2 and 5-LOX. Overall, a highly promising antiinflammatory agent was identified.
authors.affiliation: †Department of Chemistry, Guru Nanak Dev University, Amritsar, 143005, India.
authors.forename: Palwinder
authors.initials: P
authors.lastname: Singh
authors.affiliation: †Department of Chemistry, Guru Nanak Dev University, Amritsar, 143005, India.
authors.forename: Jagroop
authors.initials: J
authors.lastname: Kaur
authors.affiliation: ‡Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, 143005, India.
authors.forename: Gurjit
authors.initials: G
authors.lastname: Singh
authors.affiliation: ‡Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, 143005, India.
authors.forename: Rajbir
authors.initials: R
authors.lastname: Bhatti
mesh_terms: D000700:Analgesics / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D002151:Calorimetry; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D005260:Female; D020128:Inhibitory Concentration 50; D016859:Lipoxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D051379:Mice; D062105:Molecular Docking Simulation; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors