Bioorganic & Medicinal Chemistry 2013-03-01

Anticonvulsant evaluation of aminoalkanol derivatives of 2- and 4-methylxanthone.

Natalia Szkaradek, Agnieszka Gunia, Anna M Waszkielewicz, Lucyna Antkiewicz-Michaluk, Marek Cegła, Edward Szneler, Henryk Marona

Index: Bioorg. Med. Chem. 21(5) , 1190-8, (2013)

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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.Copyright © 2013 Elsevier Ltd. All rights reserved.