IN SILICO STUDY OF EUCALYPTOL FROM EUCALYPTUS GLOBULUS LABILL. AGAINST ANGIOTENSIN-CONVERTING ENZYME AS AN ANTIHYPERTENSIVE IN COVID-19 COMORBID

RESMI MUSTARICHIE; NYI MEKAR SAPTARINI; EDWIN PRATAMA; SANDRA MEGANTARA

doi:10.22159/ijap.2023.v15s2.25

Authors

RESMI MUSTARICHIE Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, West Java-45363, Indonesia
NYI MEKAR SAPTARINI Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, West Java-45363, Indonesia
EDWIN PRATAMA Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, West Java-45363, Indonesia
SANDRA MEGANTARA Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, West Java-45363, Indonesia

DOI:

https://doi.org/10.22159/ijap.2023.v15s2.25

Keywords:

ACE, ADMET, Antihypertensive, Eucalyptol, Eucalyptus globulus labill

Abstract

Objective: This study aimed to determine the best compound from the 62 compounds of Eucalyptus globulus Labill. as an antihypertensive based on its interaction with angiotensin-converting enzyme (ACE) using the in silico study.

Methods: The study was carried out in silico through molecular docking simulations, analysis of potential compounds using Lipinski’s rule, and ligand-based ADMET prediction on 62 compounds of the E. globulus.

Results: It was found that eucalyptol (1,8-cineole) had the best interaction with the ACE as indicated by a bond energy value (∆G) of-6.40 kcal/mol with an inhibition constant of 20.82 µM, and interacted with key amino acid residues in captopril, namely HIS513, HIS353, TYR523, and ALA354. Eucalyptol also had good physicochemical properties by fulfilling Lipinski’s rule and had the best ADMET profile compared to other compounds.

Conclusion: Eucalyptol was the best antihypertensive against ACE based on amino acid residue interaction, physicochemical properties, and ADMET profile.

Downloads

Download data is not yet available.

References

Rusiadi R, Aprilia A, Adianti V, Verawati V. Dampak COVID-19 terhadap stabilitas ekonomi dunia (studi 14 negara berdampak paling parah). J Kajian Ekon Kebijakan Publ. 2020;5(2):173.

WHO. Coronavirus (COVID-19) dashboard. Available from: https://covid19.who.int. [Last accessed on 21 Nov 2023]

Yang J, Zheng Y, Gou X, Pu K, Chen Z, Guo Q. Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. Int J Infect Dis. 2020;94:91-5. doi: 10.1016/j.ijid.2020.03.017, PMID 32173574.

Ejaz H, Alsrhani A, Zafar A, Javed H, Junaid K, Abdalla AE. COVID-19 and comorbidities: deleterious impact on infected patients. J Infect Public Health. 2020;13(12):1833-9. doi: 10.1016/j.jiph.2020.07.014, PMID 32788073.

Attique SA, Hassan M, Usman M, Atif RM, Mahboob S, Al-Ghanim KA. A molecular docking approach to evaluate the pharmacological properties of natural and synthetic treatment candidates for use against hypertension. Int J Environ Res Public Health. 2019;16(6):923-40. doi: 10.3390/ijerph16060923, PMID 30875817.

Campos JF, Berteina Raboin S. Eucalyptol, an all-purpose product. Catalysts. 2022;12(1):48-70. doi: 10.3390/catal12010048.

Igase M, Strawn WB, Gallagher PE, Geary RL, Ferrario CM. Angiotensin II AT1 receptors regulate ACE2 and angiotensin-(1-7) expression in the aorta of spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol. 2005;289(3):H1013-9. doi: 10.1152/ajpheart.00068.2005, PMID 15833808.

Guan WJ, Liang WH, Zhao Y, Liang HR, Chen ZS, Li YM. Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis. Eur Respir J. 2020;55(5):2000547. doi: 10.1183/13993003.00547-2020, PMID 32217650.

Leiva Sisnieguez CE, Espeche WG, Salazar MR. Arterial hypertension and the risk of severity and mortality of COVID-19. Eur Respir J. 2020;55(6):2001148. doi: 10.1183/13993003.01148-2020, PMID 32398296.

Biovia Discovery Studio, Comprehensive predictive science for the life sciences. Available from: https://www.3ds.com/products-services/biovia/products/molecular-modeling-simulation/biovia-discovery-studio

AutoDock. Available from: http://autodock.scripps.edu.

PreADMET. BMDRC KR. Available from: https://preadmet. [Last accessed on 21 Nov 2023]

Human angiotensin-converting enzyme in complex with phosphinic tripeptide. Available from: https://www.rcsb.org/structure/2XY9.

Xiao W, Wang D, Shen Z, Li S, Li H. Multi-body interactions in molecular docking program devised with key water molecules in protein binding sites. Molecules. 2018;23(9):2321-42. doi: 10.3390/molecules23092321, PMID 30208655.

Lipinski CA. Lead-and drug-like compounds: the rule-of-five revolution. Drug Discov Today Technol. 2004;1(4):337-41. doi: 10.1016/j.ddtec.2004.11.007, PMID 24981612.

Kenny PW. Hydrogen-bond donors in drug design. J Med Chem. 2022;65(21):14261-75. doi: 10.1021/acs.jmedchem.2c01147, PMID 36282210.

Sherman W, Beard HS, Farid R. Use of an induced fit receptor structure in virtual screening. Chem Biol Drug Des. 2006;67(1):83-4. doi: 10.1111/j.1747-0285.2005.00327.x, PMID 16492153.

Kasmawati H, Mustarichie R, Halimah E, Ruslin R, Arfan A. The identification of molecular mechanisms from bioactive compounds in Sansevieria trifasciata plant as anti-alopecia: in silico approach. Rasayan J Chem. 2022;15(2):925-32. doi: 10.31788/RJC.2022.1526731.

Trott O, Olson AJ. AutoDock vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010;31(2):455-61. doi: 10.1002/jcc.21334, PMID 19499576.

Murad HAS, Alqurashi TMA, Hussien MA. Interactions of selected cardiovascular active natural compounds with CXCR4 and CXCR7 receptors: a molecular docking, molecular dynamics, and pharmacokinetic/toxicity prediction study. BMC Complement Med Ther. 2022;22(1):35. doi: 10.1186/s12906-021-03488-8, PMID 35120520.

Bosso M, Thanaraj TA, Abu Farha M, Alanbaei M, Abubaker J, Al-Mulla F. The two faces of ACE2: the role of ACE2 receptor and its polymorphisms in hypertension and COVID-19. Mol Ther Methods Clin Dev. 2020;18:321-7. doi: 10.1016/j.omtm.2020.06.017, PMID 32665962.

Ni W, Yang X, Yang D, Bao J, Li R, Xiao Y. Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19. Crit Care. 2020;24(1):422. doi: 10.1186/s13054-020-03120-0, PMID 32660650.

Sujana D, Sumiwi SA, Saptarini NM, Levita J. ADMET prediction and molecular docking simulation of phytoconstituents in Boesenbergia rotunda rhizome with the effector caspases to understand their protective effects. Rasayan J Chem. 2022;15(4):2401-6. doi: 10.31788/RJC.2022.1547011.

Mustarichie R, Saptarini NM, Megantara S. Molecule attachment and prediction of ADMET compounds in Cinnamomum burmannii on orexin receptor as anti-insomnia. Pharmacogn J. 2022;14(3):576-83. doi: 10.5530/pj.2022.14.74.