title: Synthesis of tricyclic fused coumarin sulfonates and their inhibitory effects on LPS-induced nitric oxide and PGE2 productions in RAW 264.7 macrophages.
abstract: The regulations of NO and PGE2 productions are research topics of interest in the field of antiinflammatory drug development. In the present study, a series of tricyclic fused coumarin sulfonate derivatives was synthesized and evaluated for their abilities to inhibit NO and PGE2 productions in LPS-induced RAW 264.7 macrophages. Among all the target compounds, compound 1g possessing p-(trifluoromethyl)phenyl and fused cycloheptane moieties showed the highest inhibitory effects on NO and PGE2 productions. Compound 1g not only inhibited COX-2 activity but also reduced expressions of COX-2 and iNOS. Furthermore, ADME profiling showed that compounds 1g, 1j, 1m, and 1n are estimated to be orally bioavailable.
authors.affiliation: Korean Medical School, Kyung Hee University, Hoegi-dong, Dongdaemoon-ku, Seoul 130-701, Republic of Korea.
authors.forename: Hyeon-Lok
authors.initials: HL
authors.lastname: Jang
authors.affiliation: Center for Biomaterials, Korea Institute of Science and Technology (KIST), PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea; Department of Biomolecular Science, University of Science and Technology (UST), 113 Gwahangno, Yuseong-gu, Daejeon 305-333, Republic of Korea; Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt.
authors.forename: Mohammed I
authors.initials: MI
authors.lastname: El-Gamal
authors.affiliation: Department of Pharmaceutical Biochemistry, Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Hye-Eun
authors.initials: HE
authors.lastname: Choi
authors.affiliation: Korean Medical School, Kyung Hee University, Hoegi-dong, Dongdaemoon-ku, Seoul 130-701, Republic of Korea.
authors.forename: Ho-Yeong
authors.initials: HY
authors.lastname: Choi
authors.affiliation: Department of Pharmaceutical Biochemistry, Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea. Electronic address: ktlee@khu.ac.kr.
authors.forename: Kyung-Tae
authors.initials: KT
authors.lastname: Lee
authors.affiliation: Center for Biomaterials, Korea Institute of Science and Technology (KIST), PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea; Department of Biomolecular Science, University of Science and Technology (UST), 113 Gwahangno, Yuseong-gu, Daejeon 305-333, Republic of Korea. Electronic address: choh@kist.re.kr.
authors.forename: Chang-Hyun
authors.initials: CH
authors.lastname: Oh
mesh_terms: D000818:Animals; D002460:Cell Line; D003374:Coumarins / Q000138:chemical synthesis* / Q000494:pharmacology; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D013451:Sulfonic Acids / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D003374:Coumarins; D008070:Lipopolysaccharides; D013451:Sulfonic Acids; D009569:Nitric Oxide; C030123:coumarin; D015232:Dinoprostone
keywords: Antiinflammatory; Coumarin; Nitric oxide; PGE(2); Sulfonate; Tricyclic fused coumarin