Novel indole derivatives as melatonin receptor agonists with anticonvulsant action

Joint Event on 13^th International Conference on Biologics and Biosimilars & Biopharma & Biotherapeutics

October 24-25, 2018 | Boston, USA

Violina T Angelova, Miroslav Rangelov, Nikolay Vassilev, Pavlina Andreeva-Gateva and Jana Tchekalarova

Medical University of Sofia, Bulgaria
Institute of Organic Chemistry with Centre of Phytochemistry, Bulgaria
Bulgarian Academy of Sciences, Bulgaria

Posters & Accepted Abstracts: J Bioanal Biomed

Abstract :

The study presents a series of novel indole derivates synthesized and explored in vivo for anticonvulsant activity and neurotoxicity. The pharmacophore model was constructed according to spatial data from available drug structures targeting the MT1 receptor. Obtained model was used for the preliminary selection of potent structures for synthesis. The formation of indole hydrazideâ?? hydrazones was accomplished by the reaction of 5-methoxyindole-3-carboxaldehyde with hydrazides in the presence of ethanol. The compound with p-Cl-phenyl fragment was the most active in the 6Hz test (ED50=13.98 mg.kg-1, PI>21.46), while the derivative with 2-thienyl fragment demonstrated potency both in the MES test (ED50=108.7mg.kg-1, PI>2.76) and in the 6Hz test (ED50=96.36mg. kg-1, PI>3.11), respectively. The compound with 2-furyl fragment showed activity in the 6Hz test (ED50=38.8mg.kg-1, PI>7.89). The effects of the active compounds were higher or comparable to that of melatonin in the MES test (ED50=160.3mg.kg-1, PI>1.87) and in the 6Hz test (ED50=49.76mg.kg-1, PI>6.03), respectively. None of the compounds displayed neurotoxicity in the rota-rod test. The results suggest that the novel indole derivates deserve further evaluation in models of epilepsy and derivatization.

Biography :

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