Cardiotonic steroids as potential Na /K -ATPase inhibitors – a computational study

Patel, CN and Kumar, SP and Modi, KM and Soni, MN and Modi, NR and Pandya, HA (2019) Cardiotonic steroids as potential Na /K -ATPase inhibitors – a computational study. In: Journal of Receptors and Signal Transduction, 39 (3). pp. 226-234.

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Abstract

Cardiotonic steroids (CTS) are steroidal drugs, processed from the seeds and dried leaves of the genus Digitalis as well as from the skin and parotid gland of amphibians. The most commonly known CTS are ouabain, digoxin, digoxigenin and bufalin. CTS can be used for safer medication of congestive heart failure and other related conditions due to promising pharmacological and medicinal properties. Ouabain isolated from plants is widely utilized in in vitro studies to specifically block the sodium potassium (Na+/K+-ATPase) pump. For checking, whether ouabain derivatives are robust inhibitors of Na+/K+-ATPase pump, molecular docking simulation was performed between ouabain and its derivatives using YASARA software. The docking energy falls within the range of 8.470 kcal/mol to 7.234 kcal/mol, in which digoxigenin was found to be the potential ligand with the best docking energy of 8.470 kcal/mol. Furthermore, pharmacophore modeling was applied to decipher the electronic features of CTS. Molecular dynamics simulation was also employed to determine the conformational properties of Na+/K+-ATPase-ouabain and Na+/K+-ATPase-digoxigenin complexes with the plausible structural integrity through conformational ensembles for 100 ns which promoted digoxigenin as the most promising CTS for treating conditions of congestive heart failure patients. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.

Item Type:	Journal Article
Publication:	Journal of Receptors and Signal Transduction
Publisher:	Taylor and Francis Ltd
Additional Information:	The copyright for this article belongs to Taylor and Francis Ltd
Keywords:	adenosine triphosphatase (potassium sodium) inhibitor; bufalin; cardiotonic agent; digitoxigenin; digoxigenin; gitoxigenin; ouabagenin; ouabain; strophanthidin; unclassified drug; adenosine triphosphatase (potassium sodium); cardiac glycoside; digoxin; ligand, Article; congestive heart failure; crystal structure; dissociation constant; hydrogen bond; molecular docking; molecular dynamics; pharmacophore; quantitative structure activity relation; biological model; chemistry; diffusion; metabolism; molecular docking; reproducibility, Cardiac Glycosides; Diffusion; Digoxin; Hydrogen Bonding; Ligands; Models, Biological; Molecular Docking Simulation; Ouabain; Quantitative Structure-Activity Relationship; Reproducibility of Results; Sodium-Potassium-Exchanging ATPase
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	27 Dec 2022 10:43
Last Modified:	27 Dec 2022 10:43
URI:	https://eprints.iisc.ac.in/id/eprint/78586

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