Letters in Drug Design & Discovery

Atta-ur-Rahman  , FRS
Honorary Life Fellow
Kings College
University of Cambridge
Email: lddd@benthamscience.org


Synthesis and Anticonvulsant Activity of N-(trans)- 3-phenylprop-2-en-1-yl (Cinnamyl) Derivatives of Aminoalkanols

Author(s): Agnieszka Gunia-Krzyzak, Anna M. Waszkielewicz, Karolina Sloczynska, Magda Borczuch- Kostanska, Marek Cegla, Grzegorz Satala, Andrzej J. Bojarski and Henryk Marona

Affiliation: Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland.

Graphical Abstract:


A series of sixteen N-(trans)-3-phenylprop-2-en-1-yl (cinnamyl) derivatives of various aminoalkanols was synthesized and evaluated for anticonvulsant activity and neurotoxicity. In preliminary evaluation three standard tests in mice after intraperitoneal administration were used: maximal electroshock (MES), subcutaneous pentetrazol, and rotarod test. Fifteen compounds showed some protection in MES. Next step included evaluation in rats after oral administration. The most promising compound, (R,S)-2-{[(trans)-3-phenylprop-2-en-1-yl]amino}propan-1-ol hydrochloride (1a), was also tested in model of pilocarpine-induced status prevention, 6-Hz test, and in vitro neuroprotection evaluation. Additionally, for selected compounds experimental pKa values were determined as well as serotonin receptors (5-HT1A, 5-HT6, and 5- HT7) binding affinities were found. None of the tested compounds showed significant binding affinity to serotonin receptors. However, in vivo pharmacological results indicated that further modification of the structures might lead to discovering new potential anticonvulsants.

Keywords: Aminoalkanols, Anticonvulsant, Cinnamyl, Epilepsy, Maximal electroshock, Pentetrazol.

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Article Details

Page: [1040 - 1052]
Pages: 13
DOI: 10.2174/1570180811666140423203639