title: Anticonvulsant evaluation of aminoalkanol derivatives of 2- and 4-methylxanthone.
abstract: A series of 17 new aminoalkanol derivatives of 6-methoxy- or 7-chloro-2-methylxanthone as well as 6-methoxy-4-methylxanthone was synthesized and evaluated for anticonvulsant activity. All compounds were verified in mice after intraperitoneal (ip) administration in maximal electroshock (MES) and subcutaneous pentetrazole (scMet) induced seizures as well as neurotoxicity assessment. Eleven of the tested substances showed protection against electrically evoked seizures in the majority of the tested mice at the dose of 100 mg/kg. Additionally, one was effective at the dose of 30 mg/kg. Five substances were active at the dose of 300 mg/kg or at the dose of 100 mg/kg in the minority of the tested mice. The most promising compound revealed ED(50) value of 47.57 mg/kg in MES (mice, ip, 1h after administration) and at the same time its TD(50) was evaluated as above 400 mg/kg. Those values gave PI (calculated as TD(50)/ED(50)) of more than 8.41. Three other synthesized xanthone derivatives also proved to act as anticonvulsants and showed ED(50) values in MES test (mice, ip) ranged 80-110 mg/kg. Results were quite encouraging and suggested that in the group of xanthone derivatives new potential anticonvulsants might be found.
authors: Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland. nszkarad@cm-uj.krakow.pl
authors: Natalia
authors: N
authors: Szkaradek
authors: Agnieszka
authors: A
authors: Gunia
authors: Anna M
authors: AM
authors: Waszkielewicz
authors: Lucyna
authors: L
authors: Antkiewicz-Michaluk
authors: Marek
authors: M
authors: Cegła
authors: Edward
authors: E
authors: Szneler
authors: Henryk
authors: H
authors: Marona
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D015220:Calcium Channels / Q000737:chemistry / Q000378:metabolism; D004597:Electroshock; D007274:Injections, Intraperitoneal; D051379:Mice; D009474:Neurons / Q000187:drug effects; D010433:Pentylenetetrazole / Q000627:therapeutic use / Q000633:toxicity; D012640:Seizures / Q000188:drug therapy / Q000517:prevention & control; D013329:Structure-Activity Relationship; D044004:Xanthones / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity
chemical_list: D000927:Anticonvulsants; D015220:Calcium Channels; D044004:Xanthones; C009689:xanthone; D010433:Pentylenetetrazole