title: Toxic essential oils. Part IV: The essential oil of Achillea falcata L. as a source of biologically/pharmacologically active trans-sabinyl esters.
abstract: Herein we report on the comprehensive chemical analysis of the essential oils obtained from above- and underground parts of a previously unreported chemotype of Achillea falcata L. (Asteraceae) and, for the first time, on the biological/toxicological profile of its dominant/newly discovered volatile metabolites. Detailed spectral analyses, in combination with chemical synthesis and theoretical study, of selected constituents, enabled the identification of trans-sabinol and its esters - the formate, tiglate (new compounds), acetate, butanoate, isobutanoate, 2-methylbutanoate and 3-methylbutanoate - in both aerial and underground parts of A. falcata. Evaluation of acute toxicity in Artemia salina model, in vitro and in silico (molecular docking) evaluation of acetylcholinesterase inhibitory activity and in vivo (mice) evaluation of antinociceptive activity (hot plate, tail immersion and acetylcholine-induced abdominal writhing tests) of trans-sabinol and its esters suggested that they may interact with different targets in crustacean/mammalian organisms. Alongside moderate acute toxicity (LD50 (48 h) = 0.03-0.26 mmol/L), the tested compounds exert influence on both the peripheral and central nervous systems (in the hot plate test, trans-sabinyl tiglate, at 50 mg/kg, produced a 140% baseline increase 15 min after the treatment) and to moderately inhibit acetylcholinesterase (at the concentration of 20 µg/mL, these compounds caused a reduction of acetylcholinesterase activity up to 40%).
authors.affiliation: Department of Chemistry, Faculty of Science and Mathematics, University of Niš, Višegradska 33, 18000 Niš, Serbia. Electronic address: nikoradulovic@yahoo.com.
authors.forename: Niko S
authors.initials: NS
authors.lastname: Radulović
authors.affiliation: Department of Chemistry, Faculty of Science and Mathematics, University of Niš, Višegradska 33, 18000 Niš, Serbia.
authors.forename: Marko Z
authors.initials: MZ
authors.lastname: Mladenović
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Niš, Zorana Ðinđića 81, 18000 Niš, Serbia.
authors.forename: Pavle J
authors.initials: PJ
authors.lastname: Randjelovic
authors.affiliation: Faculty of Medicine, University of Niš, Zorana Ðinđića 81, 18000 Niš, Serbia.
authors.forename: Nikola M
authors.initials: NM
authors.lastname: Stojanović
authors.affiliation: Department of Chemistry, Faculty of Science and Mathematics, University of Niš, Višegradska 33, 18000 Niš, Serbia; Department of Chemical and Technological Sciences, State University of Novi Pazar, Vuka Karadžića bb, 36300 Novi Pazar, Serbia.
authors.forename: Milan S
authors.initials: MS
authors.lastname: Dekić
authors.affiliation: Department of Chemistry, Faculty of Science and Mathematics, University of Niš, Višegradska 33, 18000 Niš, Serbia.
authors.forename: Polina D
authors.initials: PD
authors.lastname: Blagojević
mesh_terms: D031162:Achillea / Q000737:chemistry*; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D015394:Molecular Structure; D010938:Plant Oils / Q000737:chemistry / Q000633:toxicity*; D013729:Terpenes / Q000737:chemistry / Q000633:toxicity*
chemical_list: D002800:Cholinesterase Inhibitors; D010938:Plant Oils; D013729:Terpenes
keywords: Acetylcholinesterase inhibitory activity; Achillea falcata L.; Acute toxicity; Antinociceptive activity; Essential oil; trans-Sabinol