Molecular docking of dufadienides in Bryophyllum pinnatum as potential substitutes for digoxin: inhibiting the Na/K ATPase pump in cardiac cells heart failure Omolara Adeboye 1 , Rachael Oluwatoyosi Farayola 2 1 Department of Pharmacy, University of Ibadan, Nigeria, 2 Department of Chemistry, Emmanuel Alayande University of Education, Nigeria Heart failure is a condition characterized by the heart's inability to pump enough blood to meet the body's needs, resulting in symptoms such as fatigue, shortness of breath, and fluid retention. Digoxin, a commonly prescribed medication for heart failure, improves heart function by inhibiting the Na/K ATPase pump in cardiac cells, leading to increased intracellular calcium levels and enhanced myocardial contractility. However, the narrow therapeutic index of digoxin poses a significant challenge, necessitating careful monitoring of blood levels to prevent toxicity. Moreover, digoxin's potential drug interactions can result in adverse effects and reduced effectiveness. As an alternative, bufadienolides derived from Bryophyllum pinnatum plants have emerged as promising cardiac glycosides. Phytochemicals was obtained from pubchem, geometry optimization was done on the structures of the phytochemicals to obtain the most stable conformations, IR spectroscopic parameter was done to compare the base strucutres and the functional groups using density functional theory at B3LYP/6-311G** basis set in spartan software. Sodium-potassium ATPase pump was obtained from the RCSB Protein Data Bank (PDB. The protein structure was prepared for molecular docking. Molecular docking software (PyRx), visualizer (PyMol, Biovia Discovery Studio), online databases (RCSB Protein Data Bank & Pubchem), was used to obtain the binding affinity, which was used to calculate the inhibition constant (k i ). Other pharmacokinetic parameter obtained were analazed using webserver (ADMETSar2, Molinspiration and SwissADME). Bufadienolides demonstrated favourable binding interactions with the sodium-potassium ATPase pump, similar to digoxin. Furthermore, pharmacokinetic profiling indicated a wider therapeutic index for bufadienolides, suggesting a lower risk of toxicity compared to digoxin. These findings highlight the potential of bufadienolides as alternative treatments for heart failure. References 1. Adams, K. F., Patterson, J. H., Gattis, W. A., O'Connor, C. M., Lee, C. R., & Schwartz, T. A. (2005). 2. Relationship of serum digoxin concentration to mortality and morbidity in women in the digitalis investigation group trial: a retrospective analysis. Journal of the American College of Cardiology, 46(3), 497-504. 3. American Heart Association. (2021). Heart Failure Statistics. Retrieved from https://www.heart.org/en/news/2019/05/21/ heart-failure-statistics Dallakyan, S., Olson, A.J. Small-Molecule Library Screening by Docking with PyRx. Methods Mol Biol. 2015; 1263:243-250. doi: 10.1007/978-1-4939-2269-7_19. 4. Digitalis Investigation Group. (1997). The effect of digoxin on mortality and morbidity in patients with heart failure. New England Journal of Medicine, 336(8), 525-533. Gheorghiade, M., Patel, K., & Filippatos, G. (2013). Digoxin in heart failure— where do we stand today? International Journal of Cardiology, 168(5), 4246-4249. 5. Kitchen, D. B., Decornez, H., Furr, J. R., & Bajorath, J. (2004). Docking and scoring in virtual screening for drug discovery: methods and applications. Nature Reviews Drug Discovery, 3(11), 935-949.
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