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Molecular Docking Mediated Virtual Drug Screening for GABAA Receptor: Promising Digoxin Derivatives

Year 2023, Volume: 51 Issue: 1, 71 - 91, 01.01.2023
https://doi.org/10.15671/hjbc.1139995

Abstract

In the central nervous system (CNS) of mammalian species, ℽ-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter due to it regulates neuronal development through leading neural differentiation, proliferation, migration, etc. GABAA receptor is the major GABA receptor since it has the highest expression level among the other GABA receptors within CNS. Many pieces of evidence prove that the defects in the GABAergic pathway might give rise to serious diseases such as schizophrenia, epilepsy, anxiety, depression, insomnia, etc. In this study drug library with a totally of 8170 ligands consists of three distinct datasets which are FDA-approved Drugs, Drugs Approved by World but not FDA, and Non-human Metabolites have been screened for the allosteric site of the GABAA receptor with PyRx Virtual Screening Tool and ligand-receptor interactions have been analyzed with Biovia Discovery Studio software. Results reveal that Digoxin and its two distinct derivatives (DD1 and DD2), as well as Conivaptan, are promising in the treatment of GABAergic pathway-based disorders. The findings of this report should be verified with further molecular dynamics (MD) simulations and the ligands should be tested by both in vitro and in vivo studies.

References

  • L. D. Ochoa-de la Paz, R. Gulias-Cañizo, E. D´Abril Ruíz-Leyja, H. Sánchez-Castillo, and J. Parodí, The role of GABA neurotransmitter in the human central nervous system, physiology, and pathophysiology, Rev. Mex. Neurocienc., 22 (2021) 67-76.
  • D. A. McCormick, GABA as an inhibitory neurotransmitter in human cerebral cortex, J. Neurophysiol., 62 (1989) 1018-1027.
  • A. Ghit, D. Assal, A. S. Al-shami, and D. E. E. Hussein, GABA A receptors : structure , function , pharmacology , and related disorders, J. Genet. Eng. Biotechnol., 123 (2021) 1-15.
  • A. N. Shrivastava, A. Triller, and W. Sieghart, Gaba a receptors: Post-synaptic co-localization and cross-talk with other receptors, Front. Cell. Neurosci., 5 (2011) 1-12.
  • F. C. Roth and A. Draguhn, GABA metabolism and transport: Effects on synaptic efficacy, Neural Plast., 2012 (2012) 1-12.
  • M. P. Serrano-Regal, L. Bayon-Cordero, R. P. Ordaz, E. Garay, A. Limon, R. O. Arellano, C. Matute, and M. V. Sanchez-Gomez, Expression and Function of GABA Receptors in Myelinating Cells, Front. Cell. Neurosci., 14 (2020) 1-15.
  • E. Sigel and M. E. Steinmann, Structure, function, and modulation of GABAA receptors, J. Biol. Chem., 287 (2012) 40224-40231.
  • V. Lee and J. Maguire, The impact of tonic GABAA receptor-mediated inhibition on neuronal excitability varies across brain region and cell type, Front. Neural Circuits, 8 (2014) 1-27.
  • V. Tretter and S. J. Moss, GABAA receptor dynamics and constructing GABAergic synapses, Front. Mol. Neurosci., 1 (2008) 1-13.
  • A. Scimemi, A. Andersson, J. H. Heeroma, J. Strandberg, B. Rydenhag, A. W. McEvoy, M. Thom, F. Asztely, and M. C. Walker, Tonic GABAA receptor-mediated currents in human brain, Eur. J. Neurosci., 24 (2006) 1157-1160.
  • G. Deidda, I. F. Bozarth, and L. Cancedda, Modulation of GABAergic transmission in development and neurodevelopmental disorders: Investigating physiology and pathology to gain therapeutic perspectives, Front. Cell. Neurosci., 8 (2014) 1-23.
  • B. Monesson-Olson, J. J. McClain, A. E. Case, H. E. Dorman, D. R. Turkewitz, A. B. Steiner, and G. B. Downes, Expression of the eight GABAA receptor α subunits in the developing zebrafish central nervous system, PLoS One, 13 (2018) 1-15.
  • P. L. Pearl, T. R. Hartka, J. L. Cabalza, J. Taylor, and M. K. Gibson, Inherited disorders of GABA metabolism, Future Neurol., 1 (2006) 631-636.
  • J. C. de Jonge, C. H. Vinkers, H. E. Hulshoff Pol, and A. Marsman, GABAergic mechanisms in schizophrenia: Linking postmortem and In vivo studies, Front. Psychiatry, 8 (2017) 118-130.
  • K. R. Patel, J. Cherian, K. Gohil, and D. Atkinson, Schizophrenia: Overview and treatment options, P. T., 39 (2014) 638-645.
  • T. C. Jacob, Neurobiology and Therapeutic Potential of α5-GABA Type A Receptors, Front. Mol. Neurosci., 12 (2019) 1-10.
  • E. Engin, J. Liu, and U. Rudolph, α2-containing GABAA receptors: A target for the development of novel treatment strategies for CNS disorders, Pharmacol. Ther., 136 (2012) 142-152.
  • P. Syed, N. Durisic, R. J. Harvey, P. Sah, and J. W. Lynch, Effects of GABAA Receptor α3 Subunit Epilepsy Mutations on Inhibitory Synaptic Signaling, Front. Mol. Neurosci., 13 (2020) 1-12.
  • S. K. Sanders and A. Shekhar, Regulation of anxiety by GABAA receptors in the rat amygdala, Pharmacol. Biochem. Behav., 52 (1995) 701-706.
  • M. V. Fogaça and R. S. Duman, Cortical GABAergic dysfunction in stress and depression: New insights for therapeutic interventions, Front. Cell. Neurosci., 13 (2019) 1-20.
  • D. T. Plante, J. E. Jensen, and J. W. Winkelman, The role of GABA in primary insomnia, Sleep, 35 (2012) 741-742.
  • P. Nuss, Anxiety disorders and GABA neurotransmission: A disturbance of modulation, Neuropsychiatr. Dis. Treat., 11 (2015) 165-175.
  • B. Zhang, A. Vogelzang, M. Miyajima, Y. Sugiura, Y. Wu, K. Chamoto, R. Nakano, R. Hatae, R. J. Menzies, K. Sonomura, N. Hojo, T. Ogawa, W. Kobayashi, Y. Tsutsui, S. Yamamoto, M. Maruya, S. Narushima, K. Suzuki, H. Sugiya, K. Murakami, M. Hashimoto, H. Ueno, T. Kobayashi, K. Ito, S. Fagarasan, B cell-derived GABA elicits IL-10+ macrophages to limit anti-tumour immunity, Nature, 599 (2021) 471-476.
  • H. Luo, K. Wood, F. D. Shi, F. Gao, and Y. Chang, Suramin is a novel competitive antagonist selective to α1β2γ2 GABAA over ρ1 GABAC receptors, Neuropharmacology, 141 (2018) 148-157.
  • T. Nakao and S. Banba, Broflanilide: A meta-diamide insecticide with a novel mode of action, Bioorganic Med. Chem., 24 (2016) 372-377.
  • F. J. Michel and L. E. Trudeau, Clozapine inhibits synaptic transmission at GABAergic synapses established by ventral tegmental area neurones in culture, Neuropharmacology, 39 (2000) 1536-1543.
  • M. Sahila, P. P. Babitha, S. Bandaru, A. Nayarisseri, and V. A. Doss, Molecular docking based screening of GABA (A) receptor inhibitors from plant derivatives, Bioinformation, 11 (2015) 280-289.
  • E. F. Pettersen, T. D. Goddard, C. C. Huang, G. S. Couch, D. M. Greenbatt, E. C. Meng, T. E. Ferrin, UCSF Chimera - A visualization system for exploratory research and analysis, J. Comput. Chem., 25 (2004) 1605-1612.
  • S. Dallakyan and A. Olson, Small-Molecule Library Screening by Docking with PyRx, NY: Springer New York, 1263 (2015) 243-250.
  • O. Trott and A. J. Olson, AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading, J. Comput. Chem., 31 (2010) 455-461.
  • T. Sander, Molecular Properties Prediction - Osiris Property Explorer. [Online]. Available: https://www.organic-chemistry.org/prog/peo/. [Accessed: 18-Apr-2022].
  • A. Daina, O. Michielin, and V. Zoete, SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules, Sci. Rep., 7 (2017) 1-13.
  • F. Ali, M. A. Raufi, B. Washington, and J. K. Ghali, Conivaptan: A dual receptor vasopressin V1a/V2 antagonist, Cardiovasc. Drug Rev., 25 (2007) 261-279.
  • M. Z. Hoque, P. Arumugham, N. Huda, N. Verma, M. Afiniwala, and D. H. Karia, Conivaptan: Promise of treatment in heart failure, Expert Opin. Pharmacother., 10 (2009) 2161-2169.
  • H. Van Wietmarschen, H. Hagels, R. Peters, J. Heistek, J. Van Der Greef, and M. Wang, Optimizing growth conditions for digoxin production in Digitalis lanata Ehrh, World J. Tradit. Chinese Med., 2 (2016) 24-35.
  • S. Virgadamo, Digoxin: A systematic review in atrial fibrillation, congestive heart failure and post myocardial infarction, World J. Cardiol., 7 (2015) 808-816.
  • F. H. Tan, T. L. Putoczki, S. S. Stylli, and R. B. Luwor, Ponatinib: A novel multi-tyrosine kinase inhibitor against human malignancies, Onco. Targets. Ther., 12 (2019) 635-645.
  • S. Saussele, W. Haverkamp, F. Lang, S. Koschmieder, A. Kiani, K. Jentsch-Ullrich, F. Stagelmann, H. Pfeifer, P. L. Rosee, N. Goekbuget, C. Rieger, C. F. Waller, G. N. Franke, P. le Coutre, R. Kirchmair, and C. Junghanss, Ponatinib in the Treatment of Chronic Myeloid Leukemia and Philadelphia Chromosome-Positive Acute Leukemia: Recommendations of a German Expert Consensus Panel with Focus on Cardiovascular Management, Acta Haematol., 143 (2020) 217-231.
  • S. Yoshihara, Pranlukast hydrate in the treatment of pediatric bronchial asthma, Pediatr. Heal. Med. 4 (2013) 55-63.
  • S. Tomari, T. Shimoda, T. Kawano, K. Mitsusa, Y. Obase, C. Fukusjima, H. Matsuse, and S. Kohno, Effects of pranlukast, a cysteinyl leukotriene receptor 1 antagonist, combined with inhaled beclomethasone in patients with moderate or severe asthma, Ann. Allergy, Asthma Immunol., 87 (2001) 156-161.
  • S. K. Gautam and S. K. Kulkarni, GABA/BZ-and NMDA-receptor interaction in digoxin-induced convulsions in rats, Indian J. Exp. Biol., 29 (1991) 636-640.

Moleküler Yanaştırma Yöntemiyle GABAA Reseptörü İçin Sanal İlaç Tarama: Umut Veren Digoksin Türevleri

Year 2023, Volume: 51 Issue: 1, 71 - 91, 01.01.2023
https://doi.org/10.15671/hjbc.1139995

Abstract

Memeli türlerinin merkezi sinir sisteminde (MSS) ℽ-aminobütirik asit (GABA), nöral farklılaşma, çoğalma, göç vb. yolakları düzenleyen nöronal gelişim için birincil inhibitör nörotransmiterdir. GABAA reseptörü MSS içindeki diğer GABA reseptörleri arasında en yüksek ekspresyon seviyesine sahip olduğu için majör GABA reseptörüdür. GABAerjik yolaktaki bozuklukların şizofreni, epilepsi, anksiyete, depresyon, uykusuzluk gibi ciddi hastalıklara yol açabileceğini gösteren pek çok kanıt bulunmaktadır. Bu çalışmada FDA Onaylı İlaçlar, Dünyaca Onaylı Ama FDA Onaylı Olmayan İlaçlar ve İnsan Dışı Metabolitler olarak üç farklı verisetinden oluşan toplam 8170 ligand içeren ilaç kütüphanesi GABAA reseptörünün allosterik bölgesi için PyRx Virtual Screening Tool ile taranmış ve ligand-reseptör etkileşimleri Biovia Discovery Studio yazılımı ile analiz edilmiştir. Sonuçlar, Digoksin ve iki farklı türevinin (DD1 ve DD2) ve ayrıca Conivaptan'ın GABAerjik yolak temelli bozuklukların tedavisinde umut verici olduğunu ortaya koymaktadır. Bu raporun bulguları daha ileri moleküler dinamik (MD) simülasyonları ile doğrulanmalı ve ligandlar hem in vitro hem de in vivo çalışmalarla test edilmelidir.

References

  • L. D. Ochoa-de la Paz, R. Gulias-Cañizo, E. D´Abril Ruíz-Leyja, H. Sánchez-Castillo, and J. Parodí, The role of GABA neurotransmitter in the human central nervous system, physiology, and pathophysiology, Rev. Mex. Neurocienc., 22 (2021) 67-76.
  • D. A. McCormick, GABA as an inhibitory neurotransmitter in human cerebral cortex, J. Neurophysiol., 62 (1989) 1018-1027.
  • A. Ghit, D. Assal, A. S. Al-shami, and D. E. E. Hussein, GABA A receptors : structure , function , pharmacology , and related disorders, J. Genet. Eng. Biotechnol., 123 (2021) 1-15.
  • A. N. Shrivastava, A. Triller, and W. Sieghart, Gaba a receptors: Post-synaptic co-localization and cross-talk with other receptors, Front. Cell. Neurosci., 5 (2011) 1-12.
  • F. C. Roth and A. Draguhn, GABA metabolism and transport: Effects on synaptic efficacy, Neural Plast., 2012 (2012) 1-12.
  • M. P. Serrano-Regal, L. Bayon-Cordero, R. P. Ordaz, E. Garay, A. Limon, R. O. Arellano, C. Matute, and M. V. Sanchez-Gomez, Expression and Function of GABA Receptors in Myelinating Cells, Front. Cell. Neurosci., 14 (2020) 1-15.
  • E. Sigel and M. E. Steinmann, Structure, function, and modulation of GABAA receptors, J. Biol. Chem., 287 (2012) 40224-40231.
  • V. Lee and J. Maguire, The impact of tonic GABAA receptor-mediated inhibition on neuronal excitability varies across brain region and cell type, Front. Neural Circuits, 8 (2014) 1-27.
  • V. Tretter and S. J. Moss, GABAA receptor dynamics and constructing GABAergic synapses, Front. Mol. Neurosci., 1 (2008) 1-13.
  • A. Scimemi, A. Andersson, J. H. Heeroma, J. Strandberg, B. Rydenhag, A. W. McEvoy, M. Thom, F. Asztely, and M. C. Walker, Tonic GABAA receptor-mediated currents in human brain, Eur. J. Neurosci., 24 (2006) 1157-1160.
  • G. Deidda, I. F. Bozarth, and L. Cancedda, Modulation of GABAergic transmission in development and neurodevelopmental disorders: Investigating physiology and pathology to gain therapeutic perspectives, Front. Cell. Neurosci., 8 (2014) 1-23.
  • B. Monesson-Olson, J. J. McClain, A. E. Case, H. E. Dorman, D. R. Turkewitz, A. B. Steiner, and G. B. Downes, Expression of the eight GABAA receptor α subunits in the developing zebrafish central nervous system, PLoS One, 13 (2018) 1-15.
  • P. L. Pearl, T. R. Hartka, J. L. Cabalza, J. Taylor, and M. K. Gibson, Inherited disorders of GABA metabolism, Future Neurol., 1 (2006) 631-636.
  • J. C. de Jonge, C. H. Vinkers, H. E. Hulshoff Pol, and A. Marsman, GABAergic mechanisms in schizophrenia: Linking postmortem and In vivo studies, Front. Psychiatry, 8 (2017) 118-130.
  • K. R. Patel, J. Cherian, K. Gohil, and D. Atkinson, Schizophrenia: Overview and treatment options, P. T., 39 (2014) 638-645.
  • T. C. Jacob, Neurobiology and Therapeutic Potential of α5-GABA Type A Receptors, Front. Mol. Neurosci., 12 (2019) 1-10.
  • E. Engin, J. Liu, and U. Rudolph, α2-containing GABAA receptors: A target for the development of novel treatment strategies for CNS disorders, Pharmacol. Ther., 136 (2012) 142-152.
  • P. Syed, N. Durisic, R. J. Harvey, P. Sah, and J. W. Lynch, Effects of GABAA Receptor α3 Subunit Epilepsy Mutations on Inhibitory Synaptic Signaling, Front. Mol. Neurosci., 13 (2020) 1-12.
  • S. K. Sanders and A. Shekhar, Regulation of anxiety by GABAA receptors in the rat amygdala, Pharmacol. Biochem. Behav., 52 (1995) 701-706.
  • M. V. Fogaça and R. S. Duman, Cortical GABAergic dysfunction in stress and depression: New insights for therapeutic interventions, Front. Cell. Neurosci., 13 (2019) 1-20.
  • D. T. Plante, J. E. Jensen, and J. W. Winkelman, The role of GABA in primary insomnia, Sleep, 35 (2012) 741-742.
  • P. Nuss, Anxiety disorders and GABA neurotransmission: A disturbance of modulation, Neuropsychiatr. Dis. Treat., 11 (2015) 165-175.
  • B. Zhang, A. Vogelzang, M. Miyajima, Y. Sugiura, Y. Wu, K. Chamoto, R. Nakano, R. Hatae, R. J. Menzies, K. Sonomura, N. Hojo, T. Ogawa, W. Kobayashi, Y. Tsutsui, S. Yamamoto, M. Maruya, S. Narushima, K. Suzuki, H. Sugiya, K. Murakami, M. Hashimoto, H. Ueno, T. Kobayashi, K. Ito, S. Fagarasan, B cell-derived GABA elicits IL-10+ macrophages to limit anti-tumour immunity, Nature, 599 (2021) 471-476.
  • H. Luo, K. Wood, F. D. Shi, F. Gao, and Y. Chang, Suramin is a novel competitive antagonist selective to α1β2γ2 GABAA over ρ1 GABAC receptors, Neuropharmacology, 141 (2018) 148-157.
  • T. Nakao and S. Banba, Broflanilide: A meta-diamide insecticide with a novel mode of action, Bioorganic Med. Chem., 24 (2016) 372-377.
  • F. J. Michel and L. E. Trudeau, Clozapine inhibits synaptic transmission at GABAergic synapses established by ventral tegmental area neurones in culture, Neuropharmacology, 39 (2000) 1536-1543.
  • M. Sahila, P. P. Babitha, S. Bandaru, A. Nayarisseri, and V. A. Doss, Molecular docking based screening of GABA (A) receptor inhibitors from plant derivatives, Bioinformation, 11 (2015) 280-289.
  • E. F. Pettersen, T. D. Goddard, C. C. Huang, G. S. Couch, D. M. Greenbatt, E. C. Meng, T. E. Ferrin, UCSF Chimera - A visualization system for exploratory research and analysis, J. Comput. Chem., 25 (2004) 1605-1612.
  • S. Dallakyan and A. Olson, Small-Molecule Library Screening by Docking with PyRx, NY: Springer New York, 1263 (2015) 243-250.
  • O. Trott and A. J. Olson, AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading, J. Comput. Chem., 31 (2010) 455-461.
  • T. Sander, Molecular Properties Prediction - Osiris Property Explorer. [Online]. Available: https://www.organic-chemistry.org/prog/peo/. [Accessed: 18-Apr-2022].
  • A. Daina, O. Michielin, and V. Zoete, SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules, Sci. Rep., 7 (2017) 1-13.
  • F. Ali, M. A. Raufi, B. Washington, and J. K. Ghali, Conivaptan: A dual receptor vasopressin V1a/V2 antagonist, Cardiovasc. Drug Rev., 25 (2007) 261-279.
  • M. Z. Hoque, P. Arumugham, N. Huda, N. Verma, M. Afiniwala, and D. H. Karia, Conivaptan: Promise of treatment in heart failure, Expert Opin. Pharmacother., 10 (2009) 2161-2169.
  • H. Van Wietmarschen, H. Hagels, R. Peters, J. Heistek, J. Van Der Greef, and M. Wang, Optimizing growth conditions for digoxin production in Digitalis lanata Ehrh, World J. Tradit. Chinese Med., 2 (2016) 24-35.
  • S. Virgadamo, Digoxin: A systematic review in atrial fibrillation, congestive heart failure and post myocardial infarction, World J. Cardiol., 7 (2015) 808-816.
  • F. H. Tan, T. L. Putoczki, S. S. Stylli, and R. B. Luwor, Ponatinib: A novel multi-tyrosine kinase inhibitor against human malignancies, Onco. Targets. Ther., 12 (2019) 635-645.
  • S. Saussele, W. Haverkamp, F. Lang, S. Koschmieder, A. Kiani, K. Jentsch-Ullrich, F. Stagelmann, H. Pfeifer, P. L. Rosee, N. Goekbuget, C. Rieger, C. F. Waller, G. N. Franke, P. le Coutre, R. Kirchmair, and C. Junghanss, Ponatinib in the Treatment of Chronic Myeloid Leukemia and Philadelphia Chromosome-Positive Acute Leukemia: Recommendations of a German Expert Consensus Panel with Focus on Cardiovascular Management, Acta Haematol., 143 (2020) 217-231.
  • S. Yoshihara, Pranlukast hydrate in the treatment of pediatric bronchial asthma, Pediatr. Heal. Med. 4 (2013) 55-63.
  • S. Tomari, T. Shimoda, T. Kawano, K. Mitsusa, Y. Obase, C. Fukusjima, H. Matsuse, and S. Kohno, Effects of pranlukast, a cysteinyl leukotriene receptor 1 antagonist, combined with inhaled beclomethasone in patients with moderate or severe asthma, Ann. Allergy, Asthma Immunol., 87 (2001) 156-161.
  • S. K. Gautam and S. K. Kulkarni, GABA/BZ-and NMDA-receptor interaction in digoxin-induced convulsions in rats, Indian J. Exp. Biol., 29 (1991) 636-640.
There are 41 citations in total.

Details

Primary Language English
Subjects Engineering
Journal Section Research Article
Authors

Hüseyin Saygın Portakal 0000-0002-3582-4152

Publication Date January 1, 2023
Acceptance Date October 8, 2022
Published in Issue Year 2023 Volume: 51 Issue: 1

Cite

APA Portakal, H. S. (2023). Molecular Docking Mediated Virtual Drug Screening for GABAA Receptor: Promising Digoxin Derivatives. Hacettepe Journal of Biology and Chemistry, 51(1), 71-91. https://doi.org/10.15671/hjbc.1139995
AMA Portakal HS. Molecular Docking Mediated Virtual Drug Screening for GABAA Receptor: Promising Digoxin Derivatives. HJBC. January 2023;51(1):71-91. doi:10.15671/hjbc.1139995
Chicago Portakal, Hüseyin Saygın. “Molecular Docking Mediated Virtual Drug Screening for GABAA Receptor: Promising Digoxin Derivatives”. Hacettepe Journal of Biology and Chemistry 51, no. 1 (January 2023): 71-91. https://doi.org/10.15671/hjbc.1139995.
EndNote Portakal HS (January 1, 2023) Molecular Docking Mediated Virtual Drug Screening for GABAA Receptor: Promising Digoxin Derivatives. Hacettepe Journal of Biology and Chemistry 51 1 71–91.
IEEE H. S. Portakal, “Molecular Docking Mediated Virtual Drug Screening for GABAA Receptor: Promising Digoxin Derivatives”, HJBC, vol. 51, no. 1, pp. 71–91, 2023, doi: 10.15671/hjbc.1139995.
ISNAD Portakal, Hüseyin Saygın. “Molecular Docking Mediated Virtual Drug Screening for GABAA Receptor: Promising Digoxin Derivatives”. Hacettepe Journal of Biology and Chemistry 51/1 (January 2023), 71-91. https://doi.org/10.15671/hjbc.1139995.
JAMA Portakal HS. Molecular Docking Mediated Virtual Drug Screening for GABAA Receptor: Promising Digoxin Derivatives. HJBC. 2023;51:71–91.
MLA Portakal, Hüseyin Saygın. “Molecular Docking Mediated Virtual Drug Screening for GABAA Receptor: Promising Digoxin Derivatives”. Hacettepe Journal of Biology and Chemistry, vol. 51, no. 1, 2023, pp. 71-91, doi:10.15671/hjbc.1139995.
Vancouver Portakal HS. Molecular Docking Mediated Virtual Drug Screening for GABAA Receptor: Promising Digoxin Derivatives. HJBC. 2023;51(1):71-9.

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