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Microwave-assisted synthesis of 11-substituted-3,3-dimethyl-2,3,4,5,10,11-hexahydrodibenzo[b,e][1,4]diazepin-1-one derivatives catalysed by silica supported fluoroboric acid as potent antioxidant and anxiolytic agents

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Abstract

Keeping in view the successive attributes of benzodiazepines on the central nervous system, we have synthesized a novel series of benzodiazepine derivatives as antioxidant and anxiolytic agents. All the compounds were obtained in good yield by facile synthesis. To check their antioxidant potential, DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging assay was performed. Among all the synthetics seven derivatives (SD-3, SD-5, SD-7, SD-14, SD-18, SD-19, and SD-20) exhibited IC50 values ranging from 76 to 489 nM. These seven compounds were further evaluated to check their binding abilities towards the benzodiazepine binding site on GABAA receptors. Three best-fit ligands (SD-3, SD-14 and SD-20) were further evaluated for their anxiolytic effect by using three in vivo mice models i.e. Elevated Plus Maze, Light & Dark box, and Mirror Chamber model. The study revealed that compounds SD-3 and SD-20 showed the best anxiolytic effect as compared to standard drug diazepam even at an oral dose of 1.0 mg/kg.

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Acknowledgements

The authors are grateful to University Grants Commission (RGNF), Council of Scientific & Industrial Research (CSIR), Department of Science & Technology (WOS-A) and DST-FIST for providing funds and are also thankful to Guru Nanak Dev University, Amritsar for providing various facilities to carry out the research work.

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  1. These authors contributed equally: Kavita Bhagat, Atamjit Singh

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143005, India

    Kavita Bhagat, Atamjit Singh, Suruchi Dhiman, Jatinder Vir Singh, Gurinder Kaur, Harmandeep Kaur Gulati, Raman Kumar, Rajan Salwan, Kajal Bhagat, Harbinder Singh, Sahil Sharma & Preet Mohinder Singh Bedi

  2. University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India

    Ramandeep Kaur

  3. Department of Chemistry, Guru Nanak Dev University, Amritsar, Punjab, 143005, India

    Palwinder Singh

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  1. Kavita Bhagat
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Bhagat, K., Singh, A., Dhiman, S. et al. Microwave-assisted synthesis of 11-substituted-3,3-dimethyl-2,3,4,5,10,11-hexahydrodibenzo[b,e][1,4]diazepin-1-one derivatives catalysed by silica supported fluoroboric acid as potent antioxidant and anxiolytic agents. Med Chem Res 28, 2200–2217 (2019). https://doi.org/10.1007/s00044-019-02447-w

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