title: Synthesis, anti-inflammatory activity and modeling studies of cycloartane-type terpenes derivatives isolated from Parthenium argentatum.
abstract: The 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced edema model in mice determined the anti-inflammatory activities in vivo of argentatins A, B and D, the main cycloartenol-type triterpenes present in Parthenium argentatum. Our results showed that argentatin B (ED50=1.5×10(-4)mmol/ear) and argentatin A (ED50=2.8×10(-4)mmol/ear) were more potent anti-inflammatory agents than indomethacin (ED50=4.5×10(-4)mmol/ear), the reference drug. Based on these findings, we decided to evaluate 13 derivatives of argentatins A and B. All the derivatives showed anti-inflammatory activity in the TPA-induced edema model in mice. The most active compound was 25-nor-cycloart-3, 16-dione-17-en-24-oic acid, obtained from argentatin A (ED50=1.4×10(-4)mmol/ear). Argentatin B was assayed as inhibitor of COX-2 activity one of the key enzymes involved in the TPA assay. The results showed that argentatin B at 15μM doses inhibited 77% COX-2 activity. Docking studies suggest that argentatin B interacts with Arg 120, a key residue for COX-2 activity.
authors.affiliation: Instituto de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Circuito Exterior, Coyoacán, C. P. 04510 México, D.F., Mexico.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Romero
authors.affiliation: Instituto de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Circuito Exterior, Coyoacán, C. P. 04510 México, D.F., Mexico.
authors.forename: Adriana
authors.initials: A
authors.lastname: Martínez-Vázquez
authors.affiliation: Instituto de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Circuito Exterior, Coyoacán, C. P. 04510 México, D.F., Mexico.
authors.forename: Maribel Pineda
authors.initials: MP
authors.lastname: Herrera
authors.affiliation: Instituto de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Circuito Exterior, Coyoacán, C. P. 04510 México, D.F., Mexico.
authors.forename: Karina
authors.initials: K
authors.lastname: Martinez-Mayorga
authors.affiliation: Facultad de Ciencias Químicas, Universidad de Colima, Campus Coquimatlán, Km 9, Carr. Colima-Coquimatlán, Colima, Mexico. Electronic address: hparra@ucol.mx.
authors.forename: Hortensia
authors.initials: H
authors.lastname: Parra-Delgado
authors.affiliation: Instituto de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Circuito Exterior, Coyoacán, C. P. 04510 México, D.F., Mexico.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Pérez-Flores
authors.affiliation: Instituto de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Circuito Exterior, Coyoacán, C. P. 04510 México, D.F., Mexico. Electronic address: marvaz@servidor.unam.mx.
authors.forename: Mariano
authors.initials: M
authors.lastname: Martínez-Vázquez
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D019659:Asteraceae / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry / Q000378:metabolism; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D009569:Nitric Oxide / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013729:Terpenes / Q000737:chemistry* / Q000302:isolation & purification / Q000627:therapeutic use; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use
chemical_list: D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D013729:Terpenes; D014315:Triterpenes; C474473:argentatin B; C465304:argentatin A; D009569:Nitric Oxide; C085352:cycloartane; D051546:Cyclooxygenase 2; D013755:Tetradecanoylphorbol Acetate
keywords: Anti-inflammatory activity; Argentatins; Cycloartanes; Docking; TPA-induced mice model; Triterpenes