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Molecular docking, synthesis and anticonvulsant activity of some novel 3-(2-substituted)-4-oxothiazolidine-3-yl)-2-phenylquinazoline-4(3H)-ones

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Abstract

As the therapeutic potential of quinazolinone and thiazolidinone is well mentioned in literature for their versatile biological activities, their related toxicological profiles cannot be ignored. So, the purpose of this study is to synthesize 3-(2-substituted)-4-oxothiazolidine-3-yl)-2-phenylquinazoline-4(3H)-ones (3a–3k) and evaluate them as anticonvulsant agents. Novel series of 3a–3k were synthesized and their structures elucidated on the basis of elemental and spectral analyses. A hybrid scaffold containing quinazolinone and thiazolidinone moieties was synthesized to get the title compounds, and their in vivo anticonvulsant activities were performed by maximal electro-shock (MES) induced convulsion model at a dose of 25 mg/kg body weight. Six compounds, 3b, 3c, 3d, 3e, 3f and 3i, were found to have significant anticonvulsant activities with their durations of tonic hind limb extension ranging from 13.117 to 16.450 s and animal protection from 83 to 100%. The results were compared with the standard. All compounds exhibited good binding energies ranging from − 5.15 to − 6.13 kcal/mol with sodium channel IIA inactivation gate (PDB ID: 1BYY) in molecular docking study; amongst them, 3d has shown significant binding energy of − 6.13 kcal/mol. The obtained result showed that biologically active compounds could be used as a template for future design, optimization and investigation for producing more active analogs.

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Acknowledgement

The authors are grateful to the Head, Central Instrumentation Facility (CIF) department, Savitribai Phule Pune University, Pune, India for providing the facilities for Spectral Analysis of compounds.

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Authors and Affiliations

  1. Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Sant Tukaram Nagar, Pimpri, Pune, 411018, Maharashtra, India

    Sampada S. Jangam, Sagar B. Wankhede & Sohan S. Chitlange

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  1. Sampada S. Jangam
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  2. Sagar B. Wankhede
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  3. Sohan S. Chitlange
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Correspondence to Sampada S. Jangam.

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Jangam, S.S., Wankhede, S.B. & Chitlange, S.S. Molecular docking, synthesis and anticonvulsant activity of some novel 3-(2-substituted)-4-oxothiazolidine-3-yl)-2-phenylquinazoline-4(3H)-ones. Res Chem Intermed 45, 471–486 (2019). https://doi.org/10.1007/s11164-018-3612-9

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