title: Evaluation of anti-inflammatory and analgesic effects of synthesized derivatives of ibuprofen.
abstract: Inflammatory and pain are major areas for drug discovery. Current analgesic drugs often cause a number of side-effects. In the present study, we modified carboxylic acid group of ibuprofen, one of non-steroidal anti-inflammatory drugs, based on the common structure of transient receptor potential vanilloid type 1 antagonists which are considered as new candidates for analgesic drugs, and synthesized several derivatives of ibuprofen. Comprehensive evaluations of the pharmacological properties of these compounds were investigated. Compound 17 showed weak cyclooxygenase inhibition and exhibited strong transient receptor potential vanilloid type 1 antagonistic activity. It was found to be capable of blocking noxious thermal nociception and capsaicin-induced nociception in mice. Besides, 17 showed less ulcerogenic action than ibuprofen did and had no hyperthermia side-effect compared with common transient receptor potential vanilloid type 1 antagonists. Therefore, it suggested that 17 could be used as a safe alternative analgesic candidate for pain treatment.
authors.affiliation: State Key Laboratory of Natural Medicines, Center of Drug Discovery, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.
authors.forename: Jingjie
authors.initials: J
authors.lastname: Wang
authors.forename: Dongyan
authors.initials: D
authors.lastname: Dai
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Qiu
authors.forename: Xin
authors.initials: X
authors.lastname: Deng
authors.forename: Haiyan
authors.initials: H
authors.lastname: Lin
authors.forename: Hai
authors.initials: H
authors.lastname: Qian
authors.forename: Wenlong
authors.initials: W
authors.lastname: Huang
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D001831:Body Temperature / Q000187:drug effects; D051545:Cyclooxygenase 1 / Q000737:chemistry / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D007052:Ibuprofen / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D010146:Pain / Q000188:drug therapy; D013329:Structure-Activity Relationship; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D007052:Ibuprofen
keywords: analgesic; cyclooxygenase; hyperthermia; ibuprofen; transient receptor potential vanilloid type 1