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Synthesis, anticonvulsant activity, and molecular modeling studies of novel 1-phenyl/1-(4-chlorophenyl)-2-(1H-triazol-1-yl)ethanol ester derivatives

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Abstract

A series of new ester derivatives were synthesized by the reaction of various acids with 1-phenyl/1-(4-chlorophenyl)-2-(1H-triazol-1-yl)ethanol and in vivo screened for their anticonvulsant activity. The title compounds were screened against MES and ScM seizure tests according to a modified version of the Epilepsy Therapy Screening Program (ETSP) protocol of the National Institutes of Health (NIH). Their neurotoxic effects were evaluated by the rotarod test. All the compounds showed protection against MES and/or ScM-induced seizures at 30 mg/kg without neurotoxicity. More compounds were found active in the ScM test and at lower dose than the MES test. Physicochemical and pharmacokinetic profiles of the compounds were predicted by QikProp. Using molecular docking approach we tried to get insights into their possible anticonvulsant mechanisms.

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Acknowledgements

This research was financially supported by The Scientific and Technological Research Council of Turkey (TUBITAK) (Grant no: 114S862). This study has been partly presented on “International Conference on Pharmaceutical Chemistry, 5–8 September 2016, Frankfurt-Germany” as a poster presentation with title of “Synthesis and anticonvulsant activities of novel 1-phenyl/1-(4-chlorophenyl)-2-(1H-triazol-1-yl)ethanol ester derivative compounds.”

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  1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Karadeniz Technical University, 61080, Trabzon, Turkey

    İnci Selin Doğan

  2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Faculty of Pharmacy, Inonu University, 44280, Malatya, Turkey

    Zeynep Özdemir, İrem Bozbey & Arzu Karakurt

  3. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, 06100, Ankara, Turkey

    Suat Sari & Selma Saraç

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  1. İnci Selin Doğan
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  2. Zeynep Özdemir
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Doğan, İ.S., Özdemir, Z., Sari, S. et al. Synthesis, anticonvulsant activity, and molecular modeling studies of novel 1-phenyl/1-(4-chlorophenyl)-2-(1H-triazol-1-yl)ethanol ester derivatives. Med Chem Res 27, 2171–2186 (2018). https://doi.org/10.1007/s00044-018-2225-6

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