title: Rational design, synthesis and evaluation of chromone-indole and chromone-pyrazole based conjugates: identification of a lead for anti-inflammatory drug.
abstract: Conjugates of chromone-indole and chromone-pyrazole were screened for cyclooxygenase-2 (COX-2), cyclooxygenase-1 (COX-1) and 5-lipoxygenase (5-LOX) inhibitory activities. Compounds 8 and 9 were identified as preferred inhibitors of COX-2 over the other two enzymes. Their IC50 for COX-2 was 29 nM and 20 nM, respectively and selectivity indices (SI) for COX-2 over COX-1 was 46 and 337. NMR, mass spectral studies and molecular modelling also indicated preferential interactions of compounds 8 and 9 with COX-2. Tested on albino mice against capsaicin induced algesia, compound 8 exhibited analgesic potential comparable to diclofenac. In addition to the biological profile, the desirable physico-chemical properties of these compounds make them promising leads for anti-inflammatory drugs.
authors.affiliation: Department of Chemistry, UGC Sponsored Centre for Advanced Studies, Guru Nanak Dev University, Amritsar, Punjab 143005, India.
authors.lastname: Shaveta
authors.affiliation: Department of Chemistry, UGC Sponsored Centre for Advanced Studies, Guru Nanak Dev University, Amritsar, Punjab 143005, India.
authors.forename: Amrinder
authors.initials: A
authors.lastname: Singh
authors.affiliation: Department of Chemistry, UGC Sponsored Centre for Advanced Studies, Guru Nanak Dev University, Amritsar, Punjab 143005, India.
authors.forename: Matinder
authors.initials: M
authors.lastname: Kaur
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar 143005, India.
authors.forename: Surbhi
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar 143005, India.
authors.forename: Rajbir
authors.initials: R
authors.lastname: Bhatti
authors.affiliation: Department of Chemistry, UGC Sponsored Centre for Advanced Studies, Guru Nanak Dev University, Amritsar, Punjab 143005, India. Electronic address: palwinder_singh_2000@yahoo.com.
authors.forename: Palwinder
authors.initials: P
authors.lastname: Singh
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002211:Capsaicin; D002867:Chromones / Q000737:chemistry*; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D007211:Indoles / Q000737:chemistry*; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D010147:Pain Measurement; D011720:Pyrazoles / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002867:Chromones; D016861:Cyclooxygenase Inhibitors; D007211:Indoles; D011720:Pyrazoles; C031280:pyrazole; C030374:indole; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D002211:Capsaicin
keywords: Chromone; Cyclooxygenase-2; Indole; Inhibitors; Interactions; Pyrazole