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The Structure-Activity Relatıonships of Familiar Antiepileptic Drugs and Na+ Channels

Yıl 2022, Cilt: 9 Sayı: 2, 89 - 102, 30.06.2022

Esra Nur Çakmak Mahmut Gür Bayram Kıran

https://doi.org/10.17350/HJSE19030000259

Öz

The aim of this study is to examine the effects of drug active compounds, which are widely used in the treatment of epilepsy, on voltage-gated Na+ channels are important channels that advance the action potential in the excitation direction by molecular docking method. These molecules have been selected considering the physiopathological effect mechanisms of epilepsy disease. When the action potential is stimulated, Na+ channels allow sodium ion entry into the cell and cause epilepsy seizures. For this reason, PDB ID: 4PA6 receptor, which acts as an antagonist according to its activity on the canal in the formation of epileptic seizures, was chosen for molecular docking study. As a result of molecular docking studies; Phenytoin gave the best binding affinity for 4PA6 with a value of -7.7 kcal/mol. Other results in descending order (as kcal/mol); Mesuximide (-7.5), Remasemide (-7.3), Tiagabine (-7.1), Ethotoin and Mephenytoin (-7.0), Primidon (-6.9), Topiramate (-6.6), Oxcarbazepine and Lamotrigin (-6.3), Felbamat (-6.0), Lokosamidine (-5.9), Zonisamide (-5.8), Levetiresetam and Gabapentin (-5.7), Ethosuximide (-5.6), Trimethadion (-5.1), Valproic Acid (-5.0), Vigabatrin (-4.0), determined as.

Anahtar Kelimeler

Anticonvulsant Epilepsy Moleculer Docking Ligand Receptor

Kaynakça

  • [1] Scharfman HE. Neurobiology of Brain Disorders: biological basis of neurological and psychiatric disorders. Epilepsy. 2014; 263-261. doi: 10.1016/B978-0-12-398270-4.00017-3
  • [2] Christian E, Schmidt D. Modern management of epilepsy: a practical approach. Epilepsy & Behavior. 2008;12(4):501-539.
  • [3] Genç G, Arslan Ö, Akgün H, Bek S, Göçgil Z, Odabaşı Z. Trends in choosing conventional versus new antiepileptic drugs in epilepsy treatment. Epilepsy. 2016;22(2):61-6
  • [4] Onat F, Eşkazan E. AEİ’lar. Bora İ, Yeni SN, Gürses C (Eds). Epilepsi. İstanbul: Nobel Matbaacılık; 2008;595– 607.
  • [5] Bechi E. Efficacy and tolerability of the new antiepileptic drugs: comparison of two recent guidelines. Lancet Neurology. 2004; 3:618-621.
  • [6] Stefan H, Feuerstein TJ. Novel anticonvulsant drugs. Pharmacology and Therapeutics. 2007; 113:165-183.
  • [7] Dalangin R, Kim A, Campbell RE. The Role of Amino Acids in Neurotransmission and Fluorescent Tools for Their Detection. International journal of molecular sciences. 2020;21(17), 6197. https://doi.org/10.3390/ijms21176197
  • [8] Görgüllü A, Kırış T. Excitatory aminoacids and excitotoxicity. Türk Nöroşirürji Dergisi. 2005; cilt; 15, Sayı: 1, 33- 38.
  • [9] Siesjö BK, Memezawa H, Smith ML. Neurocytotoxicity: pharmacological implications. Gundam Clinical Pharmacolgy. 5: 755-767, 1991
  • [10] Duncan JS, Sander JW, Sisodiya SM, Walker MC. Adult Epilepsy. Lancet. 2006; 367:1087-1100.
  • [11] Lengauer T, Rarey M. Computational methods for biomolecular docking. Current Opinion Structural Biolgy. 1996;6(3):402-6.
  • [12] Scharfman HE. The neurobiology of epilepsy. Current Neurology and Neuroscience Reports. 2007; 7(4), 348–354. https://doi. org/10.1007/s11910-007-0053-z
  • [13] Schmidt D, Schachter SC. Drug treatment of epilepsy in adults. BMJ. 2004; 348-254. doi:10.1136/bmj.
  • [14] Ayala G, Matsumoto H, Gumnit R. Excitability changes and inhibitory mechanisms in neocortical neurons during seizures. Journol of Neurophysiol. 1970;33 : 73-85.
  • [15] Bora I. Epilepside Medikal Tedavi: Yeni S, Bora İGC (Eds.). Epilepsi. Nobel tıp. İstanbul; 2018. p. 639–716.
  • [16] Yılmaz M. Ratlarda pentilentetrazol ile oluşturulan epileptik nöbet modelinde topiramatın beyin kalsiyum, Ca+2ATPaz ve NMDA reseptörleri üzerine etkileri. Uzmanlık tezi, Süleyman Demirel Üniversitesi Tıp Fakültesi Nöroloji Anabilim Dalı, Isparta, 2008.
  • [17] Sarı S (Arilalkil)Azol Yapısında Yeni Oksim Ester Türevleri Üzerinde Çalışmalar: Sentez, Biyolojik Aktivite Ve Moleküler Modlleme. Doktora Tezi, Hacettepe Üniversitesi Sağlık Bilimleri Enstitüsü. Ankara, 2018.
  • [18] Moody W, Futamachi K, Prince D. Extracellular potassium activity during epileptogenesis. Experimental Neurology. 1974; 42:248-263.
  • [19] Fattore C, Perucca E. Novel medications for epilepsy. Drugs. 2011:71; 2151– 2178.
  • [20] Loscher W. Critical review of current animal Modls of seizures and epilepsy used in the discovery and development of new antiepileptic drugs, Seizure 2011:20; 359–368.
  • [21] Edafiogho IO, Ananthalakshmi KV, Kombian SB. Anticonvulsant evaluation and mechanism of action of benzylamino enaminones. Bioorg Med Chem 2006;14:5266-72
  • [22] Malik S, Bahare RS. Khan SA. Design, synthesis and anticonvulsant evaluation of N-(benzo[d]thiazol-2- ylcarbamoyl)-2- methyl-4-oxoquinazoline-3(4H)- carbothioamide derivatives: a hybrid pharmacophore approach. Eur J Med Chem 2013;67:1-13
  • [23] Oliva M, Berkovic SF, Petreu S. Sodium channels and the neurobiology of epilepsy. Epilepsia. 2012; 53(11):1849–1859.
  • [24] Rajamani R, Good AC. Ranking poses in structure-based lead discovery and optimization: current trends in scoring function development. Curr Opin Drug Discov Devel. 2007;10(3):308-15.
  • [25] Lewis RA. The Development of Molecular Modlling Programs: The Use and Limitations of Physical Modls. Gramatica P, Livingstone DJ, Davis AM (Eds.). Drug Design Strategies: Quantitative Approaches. New York: RCS Publishing; 2011.
  • [26] Koehl P, Levitt MA. Brighter future for protein structure prediction. Natural Structer Biolgy. 1999;6(2):108- 11.
  • [27] Bagneris C, DeCaen PG, Naylor CE, Pryde DC, Nobeli I, Clapham DE, Wallace BA. Prokaryotic NavMs channel as a structural and functional Modl for eukaryotic sodium channel antagonism. Proc Natl Acad Sci U S A. 2011;111, 8428-8433.
  • [28] Engelborghs S, D’hooge R, De Deyn PP. Pathophysiology of epilepsy. Acta Neurologica Belgica. 2000;100, 201-213.
  • [29] Najm S, Naureen H, Sultana K, Anwar F, Rehman S, Arshad S, Khan MM. In-silico computational analysis of [6-(2, 3-Dichlorophenyl)-1, 2, 4- Triazine-3, 5-Diamine] metal complexes on voltage gated sodium channel and dihydrofolate reductase enzyme. Pakistan Journal of Pharmaceutical Sciences. Vol.33, No.4(Suppl), July 2020, pp.1779-1786.
  • [31] Correa-Basurto J, Cuevas-Hernández RI, Phillips-Farfan BV, Martanez-Archundia M, Romo-Mancillas A, Rama¬rez-Salinas GL, Parez-Gonzalez AA, Trujillo-Ferrara J, Mendoza-Torreblanca JG. Identification of the antiepileptic racetam binding site in the synaptic vesicle protein 2A by molecular dynamics and docking simulations. Frontiers in Cellular Neuroscience, 2015;9, 1-12. doi:10.3389/fncel.2015.00125
  • [32] Shi YW, Wang J, Min FL, Bian WJ, Mao BJ, Mao Y, Qin B, Li BL. HLA Risk Alleles in Aromatic Antiepileptic Drug-Induced Maculopapular Exanthema. Front Pharmacoly. 2021:12, 671572.
  • [33] Iman M, Saadabadi A, Davood A. Docking Studies of Phthalimide Pharmacophore as a Sodium Channel Blocker. Iranian Journal of Basic Medical Sciences. 2013; 16(9): 1016–1021.

Yıl 2022, Cilt: 9 Sayı: 2, 89 - 102, 30.06.2022

Esra Nur Çakmak Mahmut Gür Bayram Kıran

https://doi.org/10.17350/HJSE19030000259

Öz

Kaynakça

  • [1] Scharfman HE. Neurobiology of Brain Disorders: biological basis of neurological and psychiatric disorders. Epilepsy. 2014; 263-261. doi: 10.1016/B978-0-12-398270-4.00017-3
  • [2] Christian E, Schmidt D. Modern management of epilepsy: a practical approach. Epilepsy & Behavior. 2008;12(4):501-539.
  • [3] Genç G, Arslan Ö, Akgün H, Bek S, Göçgil Z, Odabaşı Z. Trends in choosing conventional versus new antiepileptic drugs in epilepsy treatment. Epilepsy. 2016;22(2):61-6
  • [4] Onat F, Eşkazan E. AEİ’lar. Bora İ, Yeni SN, Gürses C (Eds). Epilepsi. İstanbul: Nobel Matbaacılık; 2008;595– 607.
  • [5] Bechi E. Efficacy and tolerability of the new antiepileptic drugs: comparison of two recent guidelines. Lancet Neurology. 2004; 3:618-621.
  • [6] Stefan H, Feuerstein TJ. Novel anticonvulsant drugs. Pharmacology and Therapeutics. 2007; 113:165-183.
  • [7] Dalangin R, Kim A, Campbell RE. The Role of Amino Acids in Neurotransmission and Fluorescent Tools for Their Detection. International journal of molecular sciences. 2020;21(17), 6197. https://doi.org/10.3390/ijms21176197
  • [8] Görgüllü A, Kırış T. Excitatory aminoacids and excitotoxicity. Türk Nöroşirürji Dergisi. 2005; cilt; 15, Sayı: 1, 33- 38.
  • [9] Siesjö BK, Memezawa H, Smith ML. Neurocytotoxicity: pharmacological implications. Gundam Clinical Pharmacolgy. 5: 755-767, 1991
  • [10] Duncan JS, Sander JW, Sisodiya SM, Walker MC. Adult Epilepsy. Lancet. 2006; 367:1087-1100.
  • [11] Lengauer T, Rarey M. Computational methods for biomolecular docking. Current Opinion Structural Biolgy. 1996;6(3):402-6.
  • [12] Scharfman HE. The neurobiology of epilepsy. Current Neurology and Neuroscience Reports. 2007; 7(4), 348–354. https://doi. org/10.1007/s11910-007-0053-z
  • [13] Schmidt D, Schachter SC. Drug treatment of epilepsy in adults. BMJ. 2004; 348-254. doi:10.1136/bmj.
  • [14] Ayala G, Matsumoto H, Gumnit R. Excitability changes and inhibitory mechanisms in neocortical neurons during seizures. Journol of Neurophysiol. 1970;33 : 73-85.
  • [15] Bora I. Epilepside Medikal Tedavi: Yeni S, Bora İGC (Eds.). Epilepsi. Nobel tıp. İstanbul; 2018. p. 639–716.
  • [16] Yılmaz M. Ratlarda pentilentetrazol ile oluşturulan epileptik nöbet modelinde topiramatın beyin kalsiyum, Ca+2ATPaz ve NMDA reseptörleri üzerine etkileri. Uzmanlık tezi, Süleyman Demirel Üniversitesi Tıp Fakültesi Nöroloji Anabilim Dalı, Isparta, 2008.
  • [17] Sarı S (Arilalkil)Azol Yapısında Yeni Oksim Ester Türevleri Üzerinde Çalışmalar: Sentez, Biyolojik Aktivite Ve Moleküler Modlleme. Doktora Tezi, Hacettepe Üniversitesi Sağlık Bilimleri Enstitüsü. Ankara, 2018.
  • [18] Moody W, Futamachi K, Prince D. Extracellular potassium activity during epileptogenesis. Experimental Neurology. 1974; 42:248-263.
  • [19] Fattore C, Perucca E. Novel medications for epilepsy. Drugs. 2011:71; 2151– 2178.
  • [20] Loscher W. Critical review of current animal Modls of seizures and epilepsy used in the discovery and development of new antiepileptic drugs, Seizure 2011:20; 359–368.
  • [21] Edafiogho IO, Ananthalakshmi KV, Kombian SB. Anticonvulsant evaluation and mechanism of action of benzylamino enaminones. Bioorg Med Chem 2006;14:5266-72
  • [22] Malik S, Bahare RS. Khan SA. Design, synthesis and anticonvulsant evaluation of N-(benzo[d]thiazol-2- ylcarbamoyl)-2- methyl-4-oxoquinazoline-3(4H)- carbothioamide derivatives: a hybrid pharmacophore approach. Eur J Med Chem 2013;67:1-13
  • [23] Oliva M, Berkovic SF, Petreu S. Sodium channels and the neurobiology of epilepsy. Epilepsia. 2012; 53(11):1849–1859.
  • [24] Rajamani R, Good AC. Ranking poses in structure-based lead discovery and optimization: current trends in scoring function development. Curr Opin Drug Discov Devel. 2007;10(3):308-15.
  • [25] Lewis RA. The Development of Molecular Modlling Programs: The Use and Limitations of Physical Modls. Gramatica P, Livingstone DJ, Davis AM (Eds.). Drug Design Strategies: Quantitative Approaches. New York: RCS Publishing; 2011.
  • [26] Koehl P, Levitt MA. Brighter future for protein structure prediction. Natural Structer Biolgy. 1999;6(2):108- 11.
  • [27] Bagneris C, DeCaen PG, Naylor CE, Pryde DC, Nobeli I, Clapham DE, Wallace BA. Prokaryotic NavMs channel as a structural and functional Modl for eukaryotic sodium channel antagonism. Proc Natl Acad Sci U S A. 2011;111, 8428-8433.
  • [28] Engelborghs S, D’hooge R, De Deyn PP. Pathophysiology of epilepsy. Acta Neurologica Belgica. 2000;100, 201-213.
  • [29] Najm S, Naureen H, Sultana K, Anwar F, Rehman S, Arshad S, Khan MM. In-silico computational analysis of [6-(2, 3-Dichlorophenyl)-1, 2, 4- Triazine-3, 5-Diamine] metal complexes on voltage gated sodium channel and dihydrofolate reductase enzyme. Pakistan Journal of Pharmaceutical Sciences. Vol.33, No.4(Suppl), July 2020, pp.1779-1786.
  • [31] Correa-Basurto J, Cuevas-Hernández RI, Phillips-Farfan BV, Martanez-Archundia M, Romo-Mancillas A, Rama¬rez-Salinas GL, Parez-Gonzalez AA, Trujillo-Ferrara J, Mendoza-Torreblanca JG. Identification of the antiepileptic racetam binding site in the synaptic vesicle protein 2A by molecular dynamics and docking simulations. Frontiers in Cellular Neuroscience, 2015;9, 1-12. doi:10.3389/fncel.2015.00125
  • [32] Shi YW, Wang J, Min FL, Bian WJ, Mao BJ, Mao Y, Qin B, Li BL. HLA Risk Alleles in Aromatic Antiepileptic Drug-Induced Maculopapular Exanthema. Front Pharmacoly. 2021:12, 671572.
  • [33] Iman M, Saadabadi A, Davood A. Docking Studies of Phthalimide Pharmacophore as a Sodium Channel Blocker. Iranian Journal of Basic Medical Sciences. 2013; 16(9): 1016–1021.
Toplam 32 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Mühendislik
Bölüm Research Articles
Yazarlar

Esra Nur Çakmak 0000-0003-4033-5190

Mahmut Gür 0000-0001-9942-6324

Bayram Kıran 0000-0001-9796-6028

Yayımlanma Tarihi 30 Haziran 2022
Gönderilme Tarihi 26 Aralık 2021
Yayımlandığı Sayı Yıl 2022 Cilt: 9 Sayı: 2

Kaynak Göster

Vancouver Çakmak EN, Gür M, Kıran B. The Structure-Activity Relatıonships of Familiar Antiepileptic Drugs and Na+ Channels. Hittite J Sci Eng. 2022;9(2):89-102.
 Kapak Resmi İndir

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