title: Design, synthesis, and anticonvulsant activity of some derivatives of xanthone with aminoalkanol moieties.
abstract: A series of new xanthone derivatives have been synthesized and evaluated for their anticonvulsant properties in the maximal electroshock, subcutaneous metrazole tests and for neurotoxicity in the rotarod in mice, i.p. and rats, p.o. Compound 9: R,S-2-{2-[(1-hydroxybutan-2-yl]amino)ethoxy}-9H-xanthen-9-one and compound 12: R,S-2-{3-[(1-hydroxybutan-2-yl)amino]propoxy}-9H-xanthen-9-one exerted activity in rats, p.o. 2 and 4 h after administration, respectively. Therefore, metabolic stability of the compounds was evaluated with use of rat microsomes, resulting in half-life t1/2136 and 108 min, respectively, indicating that either the metabolites are very active or the parent compounds exert ADME properties other than metabolism which influence the late onset of activity.
authors.affiliation: Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Waszkielewicz
authors.affiliation: Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Słoczyńska
authors.affiliation: Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Pękala
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Żmudzki
authors.affiliation: Department of Pharmacobiology, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Siwek
authors.affiliation: Department of Pharmacobiology, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Gryboś
authors.affiliation: Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Henryk
authors.initials: H
authors.lastname: Marona
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004355:Drug Stability; D006207:Half-Life; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D044004:Xanthones / Q000737:chemistry*
chemical_list: D000927:Anticonvulsants; D044004:Xanthones; C009689:xanthone
keywords: 
  MES
  ; 9H-xanthen-9-one; aminoalkanols; metabolic stability; rat microsomes; seizures; status epilepticus; xanthone