EVALUATION OF ANTICONVULSANT PROPERTIES OF NOVEL IMINE DERIVATIVES OF PIPERIDONE OXIMES: IN-SILICO AND IN-VIVO ACTIVITY IN SEIZURE MODELS
Main Article Content
Keywords
Seizures, Convulsion, Novel Anticonvulsant Agents, Piperidone Oximes, Imine derivatives
Abstract
Epileptic seizures and convulsions are widespread neurological conditions that impact a large number of people worldwide, resulting in a substantial impact on the overall disease and disability burden. Seizures occur worldwide at a rate of approximately 50 million incidents per year, and convulsions make up a significant fraction of these occurrences. These diseases are defined by abrupt and excessive electrical discharges in the brain, frequently leading to uncontrolled muscular spasms and poor consciousness. Although there have been improvements in pharmacotherapy, there is still a significant demand for novel anticonvulsant drugs that can target numerous pathways implicated in the genesis of seizures.
This study assesses the anticonvulsant efficacy of a new chemical, 3-Isopropyl-2,6-Diphenylpiperidin-4-One Oxime, using a comprehensive methodology that includes in silico docking studies and in vivo efficacy testing with a pentylenetetrazole (PTZ)-induced seizure model. Docking studies evaluated the compound's binding affinities compared to Diazepam, a widely recognized anticonvulsant medication. The results obtained from experiments on living organisms showed that 3-Isopropyl-2,6-Diphenylpiperidin-4-One Oxime effectively delayed the start of seizures and decreased their intensity. This indicates that the compound has a complex mode of action. The results emphasize the potential of 3-Isopropyl-2,6-Diphenylpiperidin-4-One Oxime as a viable option for further advancement in treating seizures and convulsions, a pressing requirement in global neurological healthcare.
References
2. Beghi, E., Giussani, G., Costa, C., DiFrancesco, J.C., Dhakar, M., Leppik, I., Kwan, P., Akamatsu, N., Cretin, B., O'Dwyer, R. and Kraemer, G., 2023. The epidemiology of epilepsy in older adults: a narrative review by the ILAE task force on epilepsy in the elderly. Epilepsia, 64(3), pp.586-601.
3. Chia, S.Y., Khor, B.K., Tay, Y.J., Liew, K.F. and Lee, C.Y., 2023. Discovery of blood-brain barrier permeant amine-functionalized aurones as inhibitors of activated microglia. Bioorganic Chemistry, 135, p.106509.
4. Dang, L.T. and Silverstein, F.S., 2017. Drug treatment of seizures and epilepsy in newborns and children. Pediatric Clinics, 64(6), pp.1291-1308.
5. Divya, B., Narayanan, J., Chitra, V. and Tamilanban, T., 2022. Evaluation of Anti-Convulsant Activity of Olivetol on Ptz Induced Seizure Model. NeuroQuantology, 20(17), p.372.
6. Kumar, A., Agarwal, P., Rathi, E. and Kini, S.G., 2022. Computer-aided identification of human carbonic anhydrase isoenzyme VII inhibitors as potential antiepileptic agents. Journal of Biomolecular Structure and Dynamics, 40(11), pp.4850-4865.
7. Malawska, B., 2005. New anticonvulsant agents. Current topics in medicinal chemistry, 5(1), pp.69-85.
8. Maloney, E.M., Chaila, E., O'Reilly, É.J. and Costello, D.J., 2020. Incidence of first seizures, epilepsy, and seizure mimics in a geographically defined area. Neurology, 95(5), pp.e576-e590.
9. Nunes-Alves, A., Ormersbach, F. and Wade, R.C., 2021. Prediction of the drug–target binding kinetics for flexible proteins by comparative binding energy analysis. Journal of Chemical Information and Modeling, 61(7), pp.3708-3721.
10. Perucca, E., Bialer, M. and White, H.S., 2023. New GABA-targeting therapies for the treatment of seizures and epilepsy: I. Role of GABA as a modulator of seizure activity and recently approved medications acting on the GABA system. CNS drugs, 37(9), pp.755-779.
11. Riney, K., Bogacz, A., Somerville, E., Hirsch, E., Nabbout, R., Scheffer, I.E., Zuberi, S.M., Alsaadi, T., Jain, S., French, J. and Specchio, N., 2022. International League Against Epilepsy classification and definition of epilepsy syndromes with onset at a variable age: a position statement by the ILAE Task Force on Nosology and Definitions. Epilepsia, 63(6), pp.1443-1474.
12. Sahoo, C.R., Paidesetty, S.K., Sarathbabu, S., Dehury, B., Senthil Kumar, N. and Padhy, R.N., 2022. Molecular dynamics simulation, synthesis and topoisomerase inhibitory actions of vanillin derivatives: a systematic computational structural integument. Journal of Biomolecular Structure and Dynamics, 40(22), pp.11653-11663.
13. Sarma, A.K., Khandker, N., Kurczewski, L. and Brophy, G.M., 2016. Medical management of epileptic seizures: challenges and solutions. Neuropsychiatric disease and treatment, pp.467-485.
14. Stefan, H.T.J.F. and Feuerstein, T.J., 2007. Novel anticonvulsant drugs. Pharmacology & therapeutics, 113(1), pp.165-183.
15. Subbaiah, M.A. and Meanwell, N.A., 2021. Bioisosteres of the phenyl ring: recent strategic applications in lead optimization and drug design. Journal of Medicinal Chemistry, 64(19), pp.14046-14128.
16. Van Erum, J., Van Dam, D. and De Deyn, P.P., 2019. PTZ-induced seizures in mice require a revised Racine scale. Epilepsy & Behavior, 95, pp.51-55.
17. Wong, I.C. and Lhatoo, S.D., 2000. Adverse reactions to new anticonvulsant drugs. Drug Safety, 23, pp.35-56.
18. Yuan, X., Fu, Z., Ji, P., Guo, L., Al-Ghamdy, A.O., Alkandiri, A., Habotta, O.A., Abdel Moneim, A.E. and Kassab, R.B., 2020. Selenium nanoparticles pre-treatment reverse behavioral, oxidative damage, neuronal loss, and neurochemical alterations in pentylenetetrazole-induced epileptic seizures in mice. International Journal of Nanomedicine, pp.6339-6353.
Article Sidebar
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All articles published in JPTCP are licensed under Copyright Creative Commons Attribution-NonCommercial 4.0 International License.
Maryam Inayat
Department of Pharmacology, Baqai Institute of Pharmaceutical Sciences, Baqai Medical University, Karachi, Pakistan
Rehana Perveen
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Baqai Medical University, Karachi, Pakistan
Zuneera Akram
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Baqai Medical University, Karachi, Pakistan
Ashok Kumar
Department of Pharmacology, Faculty of Pharmacy, University of Sindh, Jamshoro, Pakistan
Maryam Akani
Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Baqai Medical University, Karachi, Pakistan
Asma Elahi
Department of Pharmacology, Baqai Institute of Pharmaceutical Sciences, Baqai Medical University, Karachi, Pakistan
Rubina Siddiqui
Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi-75270, Pakistan
Mahwish Akhtar
Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences, Dow college of Pharmacy, Dow University of Health Sciences, Karachi, Pakistan.