title: Synthesis and anti-inflammatory activity of ent-kaurene derivatives.
abstract: A series of kaurene derivatives (1-63) were prepared and evaluated for anti-inflammatory activity. Thirteen of the tested compounds were able to inhibit NO production with an IC(50) between 2 and 10 μM. Compounds 11, 12, 14 and 23 showed low percentage of cell viability, whereas compounds 9, 10, 17, 28, 37, 48, 55, 61 and 62 were non-cytotoxic at the concentration up to 25 μM. Some structure-activity relationships were outlined. Compounds 28, 55 and 62, were selected as representative compounds and they potently inhibited the protein expression of NOS-2. We also determined that inhibition of NF-κB activation might be the mechanism involved in anti-inflammatory effects of these kaurene derivatives. As expected, cytokines IL-6, IL-1α, TNF-α and IFN-γ were downregulated in the presence of compound 28, 55 and 62 after stimulation with LPS. These results indicate that kaurene derivatives might be used for the design of new anti-inflammatory agents.
authors.affiliation: Instituto Universitario de Bio-Orgánica Antonio González, Universidad de La Laguna, Avda Astrofísico Fco Sánchez 2, 38206 La Laguna, Tenerife, Spain.
authors.forename: Idaira
authors.initials: I
authors.lastname: Hueso-Falcón
authors.forename: Irene
authors.initials: I
authors.lastname: Cuadrado
authors.forename: Florencia
authors.initials: F
authors.lastname: Cidre
authors.forename: Juan M
authors.initials: JM
authors.lastname: Amaro-Luis
authors.forename: Angel G
authors.initials: AG
authors.lastname: Ravelo
authors.forename: Ana
authors.initials: A
authors.lastname: Estevez-Braun
authors.forename: Beatriz
authors.initials: B
authors.lastname: de Las Heras
authors.forename: Sonsoles
authors.initials: S
authors.lastname: Hortelano
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D045786:Diterpenes, Kaurane / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D045786:Diterpenes, Kaurane; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009569:Nitric Oxide; C002627:kaurene; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse