Download PDF
CC BY 4.0 · Journal of Health and Allied Sciences NU
DOI: 10.1055/s-0044-1787814
Original Article

Synthesis, Molecular Docking, and Anticonvulsant Activity of 1,3,4-Oxadiazole Derivatives

Anagha Balachandra
1   Department of Pharmaceutical Chemistry, Nitte Gulabi Shetty Memorial Institute of Pharmaceutical Sciences (NGSMIPS), Nitte (Deemed to be University), Mangalore, Karnataka, India
,
Shridhar Narayan Deshpande
1   Department of Pharmaceutical Chemistry, Nitte Gulabi Shetty Memorial Institute of Pharmaceutical Sciences (NGSMIPS), Nitte (Deemed to be University), Mangalore, Karnataka, India
,
Anjana Raj
1   Department of Pharmaceutical Chemistry, Nitte Gulabi Shetty Memorial Institute of Pharmaceutical Sciences (NGSMIPS), Nitte (Deemed to be University), Mangalore, Karnataka, India
,
Bistuvalli C. Revanasiddappa
1   Department of Pharmaceutical Chemistry, Nitte Gulabi Shetty Memorial Institute of Pharmaceutical Sciences (NGSMIPS), Nitte (Deemed to be University), Mangalore, Karnataka, India
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

Abstract

A novel series of 1,3,4-oxadiazoles (O1–4) were synthesized and physical characterization was done by spectroscopic data (infrared, mass, proton nuclear magnetic resonance). To ascertain the synthesized compound's likely binding mechanism and affinity toward the protein target (Protein Data Bank ID: 3R7X), molecular docking was performed. The synthesized compounds were subjected to in silico analysis using Schrodinger suite 2020–4 and absorption, distribution, metabolism, and excretion screening. Some of the synthesized compounds were subjected to in vivo evaluation of anticonvulsant activity by maximal electroshock seizure and pentylenetetrazol model. The synthesized 1,3,4-oxadiazole analogs may be developed as lead compounds and effective anticonvulsant agents for the pharmaceutical industry based on computational and in vivo data.

Keywords

1,3,4-oxadiazoles - molecular docking - anticonvulsant activity - MES method - diazepam


Publication History

Article published online:
18 June 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

 

  • References

  • 1 Wang S, Liu H, Wang X. et al. Synthesis of 1,3,4-oxadiazole derivatives with anticonvulsant activity and their binding to the GABAA receptor. Eur J Med Chem 2020; 206: 112672
    CrossrefPubMedGoogle Scholar
  • 2 Chauhan B, Kumar R. Salahuddin, et al. Design, synthesis, in vivo, and in silico evaluation of benzothiazoles bearing a 1,3,4-oxadiazole moiety as new antiepileptic agents. ACS Omega 2023; 8 (02) 2520-2530
    CrossrefPubMedGoogle Scholar
  • 3 Beghi E. The epidemiology of epilepsy. Neuroepidemiology 2020; 54 (02) 185-191
    CrossrefPubMedGoogle Scholar
  • 4 Singh H, Kumar R, Mazumder A. et al. Design, synthesis, in vivo and in silico evaluation of novel benzothiazole-hydrazone derivatives as new antiepileptic agents. Med Chem Res 2022; 31 (09) 1431-1447
    CrossrefGoogle Scholar
  • 5 Abou-Khalil BW. Update on antiepileptic drugs 2019. Continuum (Minneap Minn) 2019; 25 (02) 508-536
    Google Scholar
  • 6 Baulac M, Rosenow F, Toledo M. et al. Efficacy, safety, and tolerability of lacosamide monotherapy versus controlled-release carbamazepine in patients with newly diagnosed epilepsy: a phase 3, randomised, double-blind, non-inferiority trial. Lancet Neurol 2017; 16 (01) 43-54
    CrossrefPubMedGoogle Scholar
  • 7 Sangshetti JN, Chabukswar AR, Shinde DB. Microwave assisted one pot synthesis of some novel 2,5-disubstituted 1,3,4-oxadiazoles as antifungal agents. Bioorg Med Chem Lett 2011; 21 (01) 444-448
    CrossrefPubMedGoogle Scholar
  • 8 Boström J, Hogner A, Llinàs A, Wellner E, Plowright AT. Oxadiazoles in medicinal chemistry. J Med Chem 2012; 55 (05) 1817-1830
    CrossrefPubMedGoogle Scholar
  • 9 Jnyanaranjan P, Jagannath VP, Chandra SP, Jitendriya M. Synthesis, characterization, antibacterial and analgesic evaluation of some 1,3,4-oxadiazole derivatives. Pharma Chem 2011; 3 (02) 485-490
    Google Scholar
  • 10 Sasmita D, Ashok KB, Jagadish SB, Maiti C, Maity TK. Synthesis of some novel 3,5-disubstituted 1,3,4-oxadiazole derivatives and anticancer activity on EAC animal model. Med Chem Res 2011; 20 (08) 1206-1213
    CrossrefGoogle Scholar
  • 11 Gamal El-Din MM, El-Gamal MI, Abdel-Maksoud MS, Yoo KH, Oh CH, Chang HO. Synthesis and in vitro antiproliferative activity of new 1,3,4-oxadiazole derivatives possessing sulfonamide moiety. Eur J Med Chem 2015; 90: 45-52
    CrossrefPubMedGoogle Scholar
  • 12 Adimule V, Medapa S, Adarsha HJ, Kumar SL, Rao PK. Design, synthesis and cytotoxic evaluation of novel 2(4-N,N-Dimethyl) pyridine containing 1,3,4-oxadiazole moiety. Asian J Biomed Pharm Sci 2015; 4 (37) 1-5
    Google Scholar
  • 13 Sushil KK, Vivek G, Varsha K, Mishra P, Stables JP, Jain NK. Anticonvulsant and sedative-hypnotic activity of some novel 3-[5-(4-substituted) phenyl-1,3,4-oxadiazole-2yl]-2-styrylquinazoline-4(3H)-ones. Med Chem Res 2010; 19 (03) 250-261
    CrossrefGoogle Scholar
  • 14 Shyma PC, Balakrishna K, Peethambar SK, Vijesh AM. Synthesis, characterization, antidiabetic and antioxidant activity of 1,3,4-oxadiazole derivatives bearing 6-methyl pyridine moiety. Pharma Chem 2015; 7 (12) 137-145
    Google Scholar
  • 15 Revanasiddappa BC, Subrahmanyam EVS, Satyanarayana D. Synthesis and biological evaluation of 2-aryl-5(8-quinolonoxymethyl) 1, 3, 4-oxadiazoles. Ind J Het Chem 2009; 18 (02) 403-404
    Google Scholar
  • 16 Prasanna KBN, Mohana KN, Mallesha L. Synthesis of N-[{5-Aryl-1,3,4-oxadiazole-2-yl}methyl]-4-methoxyaniline derivatives and their anticonvulsant activity. J Chem 2013; •••: 1-7
    CrossrefGoogle Scholar
  • 17 Malkaje S, Srinivasa MG, Deshpande N S, Navada S, Revanasiddappa Bc. An In-silico approach: design, homology modeling, molecular docking, MM/GBSA simulations, and ADMET screening of novel 1,3,4-oxadiazoles as PLK1 inhibitors. Curr Drug Res Rev 2023; 15 (01) 88-100
    CrossrefPubMedGoogle Scholar
  • 18 Deshpande S, Mahendra GM, Aggarwal NN, Revanasiddappa BC. Insilico design, ADMET screening, MM-GBSA binding free energy of novel 1,3,4 oxadiazoles linked Schiff bases as PARP-1 inhibitors targeting breast cancer. Future J Pharm Sci 2021; 7: 174-183
    CrossrefGoogle Scholar
  • 19 Aggarwal NN, Revanasiddappa BC, Gatpoh BFD, Kumar V, Kumar H. Synthesis, in silico analysis and anticonvulsant activity of novel pyrimidine derivatives. Indian Drugs 2021; 58 (05) 21-29
    CrossrefGoogle Scholar