An Insight Into The Evaluation of The Interaction of Escitalopram And Aspirin With Dispersion-corrected And Dispersion-free Functionals: DFT And QTAIM Analyses

Year 2025, Volume: 38 Issue: 4, 1721 - 1730, 01.12.2025

Musa Daboe , Cemal Parlak , Özge Bağlayan , Özgür Alver

https://doi.org/10.35378/gujs.1635565

Abstract

In some cases, it seems an unavoidable preference to use more than one drug at once for the treatment of multiple health problems. At this point drug-drug interactions in which some cases might produce toxic effects for patients must be considered. In present work, we have computationally examined, the outcomes of possible interaction between escitalopram and aspirin for the cases when they are used together. The electronic, structural and IR spectroscopic behaviors of the interacted drug system were also analyzed. The importance of dispersion-corrected and dispersion-free functionals for the calculations of binding energies was examined. While the value of the strongest binding interaction was found as -15.07 kcal/mol with M062X functional, B3LYP produced the weakest interaction with a value of -0.60 kcal/mol. The results of this study show that escitalopram and aspirin tend to interact to some extent resulting in some structural and electronic observable alterations. Henceforth, it is suggested that special attention and further experimental studies are required to enlighten the exact effect of this interaction when using these drugs together.

Keywords

Escitalopram , Aspirin , Dispersive energy correction , Drug-drug interactions

References

• [1] Seymour, R.M., Routledge, P.A., “Important Drug-Drug Interactions in the Elderly”, Drugs Aging, 12(6): 485–494, (1998). DOI: https://doi.org/10.2165/00002512-199812060-00006
• [2] Arayne, M.S., Sultana, N., Shamshad, H., Mirza, A.Z., “Drug interaction studies of gliquidone with fexofenadine, cetirizine, and levocetirizine”, Medicinal Chemistry Research, 19: 1064–1073, (2010). DOI: https://doi.org/10.1007/s00044-009-9252-2
• [3] Flynn, E., “Drug-Drug Interactions”, xPharm: The Comprehensive Pharmacology Reference, Editor: Enna, S.J., Bylund, D.B., Boston: Elsevier, (2007).
• [4] Uno, M., Nakamura, Y., Yamashita, F., “Application of machine learning techniques in population pharmacokinetics/pharmacodynamics modeling”, Drug Metabolism and Pharmacokinetics, 56: 101004, (2024). DOI: https://doi.org/10.1016/j.dmpk.2024.101004
• [5] Doherty, M., Hawkey, C., Goulder, M., Gibb, I., Hill, N., Aspley, S., Reader, S., “A randomised controlled trial of ibuprofen, paracetamol or a combination tablet of ibuprofen/paracetamol in community-derived people with knee pain”, Annals of Rheumatic Disease, 70: 1534–1541, (2011). DOI: https://doi.org/10.1136/ard.2011.154047
• [6] Zhang, L., Wang, X., Wang, L., Badawy, S., Liu, Z., Xie, C., Wang, X., Tao, Y., “A new drug-drug interaction-tilmicosin reduces the metabolism of enrofloxacin through CYP3A4”, Research in Veterinary Science, 148: 33–41, (2022). DOI: https://doi.org/10.1016/j.rvsc.2022.05.004
• [7] Casanova, F., Santos, L., “Encapsulation of cosmetic active ingredients for topical application– a review”, Journal of Microencapsulation, 33(1): 1–17, (2016). DOI: 10.3109/02652048.2015.1115900
• [8] Daboe, M., Parlak, C., Alver, Ö., “Density Functional, “Investigation on Drug-Drug Interactions: Escitalopram and Salicylicacid”, Eskişehir Teknik Üniversitesi, Bilim ve Teknoloji Dergisi B-Teorik Bilimler, 11(1): 36–42, (2023). DOI: https://doi.org/10.20290/estubtdb.1119287
• [9] Cadavid, A.P., “Aspirin: The Mechanism of Action Revisited in the Context of Pregnancy Complications”, Frontiers in Immunology, 15(8): 261, (2017). DOI: 10.3389/fimmu.2017.00261
• [10] Paseban, M., Marjaneh, R.M., Banach, M., Matbou Riahi, M., Bo, S., Sahebkar, A., “Modulation of microRNAs by aspirin in cardiovascular disease”, Trends in Cardiovascular Medicine, 30(5): 249–254, (2020). DOI: 10.1016/j.tcm.2019.08.005
• [11] Rolnik, D.L., Nicolaides, K.H., Poon, L.C., “Prevention of preeclampsia with aspirin”, American Journal of Obstetrics and Gynecology, 226(2): 1108–1119, (2022). DOI: 10.1016/j.ajog.2020.08.045
• [12] Rolnik, D.L., Wright, D., Poon, L.C., O’Gorman, N., Syngelaki, A., de Paco Matallana, C., Akolekar, R., Cicero, S., Janga, D., Singh, M., Molina, F.S., Persico, N., Jani, J.C., Plasencia, W., Papaioannou, G., Tenenbaum-Gavish, K., Meiri, H., Gizurarson, S., Maclagan, K., Nicoladies, K.H., “Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia”, New England Journal of Medicine, 377(7): 613–622, (2017). DOI: 10.1056/NEJMoa1704559
• [13] Zhang, X., Du, R., Luo, N., Xiang, R., Shen, W., “Aspirin mediates histone methylation that inhibits inflammation-related stemness gene expression to diminish cancer stemness via COX-independent manner”, Stem Cell Research & Therapy, 11(1): 370, (2020). DOI: 10.1186/s13287-020-01884-4
• [14] Hasin, D.S., Sarvet, A.L., Meyers, J.L., Saha, T.D., Ruan, W.J., Stohl, M., Grant, B.F., “Epidemiology of adult DSM-5 major depressive disorder and its specifiers in the United States”, JAMA Psychiatry, 75(4): 336–346, (2018). DOI: 10.1001/jamapsychiatry.2017.4602
• [15] Otte, C., Gold, S.M., Penninx, B.W., Pariante, C.M., Etkin, A., Fava, M., Mohr, D.C., Schatzberg, A.F., “Major depressive disorder”, Nature Reviews Disease Primers, 2: 16065, (2016). DOI: 10.1038/nrdp.2016.65
• [16] Owens, M.J., Knight, D.L., Nemeroff, C.B., “Second-generation SSRIs: human monoamine transporter binding profile of escitalopram and R-fluoxetine”, Biological Psychiatry, 50: 345–350, (2001). DOI: 10.1016/s0006-3223(01)01145-3
• [17] Davidson, J.R.T., Bose, A., Korotzer, A., Zheng, H., “Escitalopram in the treatment of generalized anxiety disorder: double-blind, placebo controlled, flexible-dose study”, Depression and Anxiety, 19: 234─240, (2004). DOI: 10.1002/da.10146
• [18] Cipriani, A., Furukawa, T.A., Salanti, G., Chaimani, A., Atkinson, L.Z., Ogawa, Y., Leucht, S., Ruhe, H.G., Turner, E.H., Higgins, J.P.T., Egger, M., Takeshima, N., Hayasaka, Y., Imai, H., Shinohara, K., Tajika, A., Ioannidis, J.P.A., Geddes, J.R., “Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis”, Lancet, 391: 1357–1366, (2018). DOI: 10.1016/S0140-6736(17)32802-7
• [19] Yuet, W.C., Derasari, D., Sivoravong, J., Mason, D., Jann, M., “Selective serotonin reuptake inhibitor use and risk of gastrointestinal and intracranial bleeding”, The Journal of the American Osteopathic Association, 119(2): 102–111, (2019). DOI: 10.7556/jaoa.2019.016
• [20] Andrade, C., Sandarsh, S., Chethan, K.B., Nagesh, K.S., “Serotonin reuptake inhibitor antidepressants and abnormal bleeding: a review for clinicians and a reconsideration of mechanisms”, The Journal of Clinical Psychiatry, 71(12): 1565–1575, (2010). DOI: 10.4088/JCP.09r05786blu
• [21] de Abajo, F.J., García-Rodríguez, L.A., “Risk of upper gastrointestinal tract bleeding associated with selective serotonin reuptake inhibitors and venlafaxine therapy: interaction with nonsteroidal anti-inflammatory drugs and effect of acid-suppressing agents”, Archives of General Psychiatry, 65(7): 795–803, (2008). DOI: 10.1001/archpsyc.65.7.795
• [22] Parlak, C., Alver, Ö., Bağlayan, Ö., “Quantum mechanical simulation of Molnupiravir drug interaction with Si-doped C60 fullerene”, Computational and Theoretical Chemistry, 1202: 113336, (2021). DOI: https://doi.org/10.1016/j.comptc.2021.113336
• [23] Al-Hazmi, G.H., Ibrahim, A.A., Refat, M.S., Adam, F.A., Allam, A., Shakya, S., Alsuhaibani, A.M., “Intermolecular charge-transfer complexes between chlorothiazide antihypertensive drug against iodine sigma and picric acid pi acceptors: DFT and molecular docking interaction study with Covid-19 protease”, Journal of the Indian Chemical Society, 99: 100605, (2022). DOI: https://doi.org/10.1016/j.jics.2022.100605
• [24] Sunny, S.A., Jose E., Tomlal, Thomas, R., “Exploring non-covalent interactions: A computational study of methyl acetate in chloroform and hexafluoroisopropanol”, Chemical Physics Impact, 8: 100514, (2024). DOI: https://doi.org/10.1016/j.chphi.2024.100514
• [25] Rajimon, K.J., Abdullah Alzahrani, A.Y., Thangaiyan, P., Thomas, R. “Design, Synthesis, Biocompatibility, molecular docking and molecular dynamics studies of novel Benzo[b]thiophene-2-carbaldehyde derivatives targeting human IgM Fc Domains”, Bioorganic Chemistry, 156: 108206, (2025). DOI: https://doi.org/10.1016/j.bioorg.2025.108206
• [26] Bader, R.F.W., “In Atoms in Molecules: A Quantum Theory”, (Oxford: Clarendon Press), (1990).
• [27] Rozas, I., Alkorta, I., Elguero, J., “Behavior of Ylides Containing N, O, and C Atoms as Hydrogen Bond Acceptors”, Journal of the American Chemical Society, 122: 11154–11161, (2000). DOI: https://doi.org/10.1021/ja0017864
• [28] Rostami, Z., Hosseinian, A., Monfared, A., “DFT results against experimental data for electronic properties of C60 and C70 fullerene derivatives”, Journal of Molecular Graphics and Modelling, 81: 60–67, (2018). DOI: https://doi.org/10.1016/j.jmgm.2018.02.009
• [29] Alrawashdeh, A.I., Lagowski, J.B., “The role of the solvent and the size of the nanotube in the non-covalent dispersion of carbon nanotubes with short organic oligomers – a DFT study”, RSC Advances, 8: 30520, (2018). DOI: 10.1039/c8ra02460j
• [30] Chai, J.D., Head-Gordon, M., “Long-range corrected hybrid density functionals with damped atom-atom dispersion corrections”, A European Journal of Physical Chemistry Chemical Physics, 10: 6615–6620, (2008). DOI https://doi.org/10.1039/B810189B
• [31] Omurtag Özgen, P.S., Durmaz, H., Parlak, C., Alver, Ö., Bağlayan, Ö., “Non-covalent functionalization of single walled carbon nanotubes with pyrene pendant polyester: A DFT supported study”, Journal of Molecular Structure, 1209: 127943, (2020). DOI: https://doi.org/10.1016/j.molstruc.2020.127943
• [32] Lu, T., Chen, F. “Multiwfn: a multifunctional wavefunction analyzer”, Journal of Computational Chemistry, 33: 580–592, (2012). DOI: https://doi.org/10.1002/jcc.22885
• [33] Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Scalmani, G., Barone, V., Mennucci, B., Petersson, G.A., Nakatsuji, H., Caricato, M., Li, X., Hratchian, H.P., Izmaylov, A.F., Bloino, J., Zheng, G., Sonnenberg, J.L., Hada, M., Ehara, M., Toyota, K., Fukuda, R., Hasegawa, J., Ishida, M., et al., Gaussian 09, Gaussian Inc., Wallingford, CT, (2009).
• [34] Dennington, R.D., Keith, T.A., Millam, J.M., GaussView 5.0.8, Gaussian Inc., (2008).
• [35] Peyghan, A.A., Soltani, A., Pahlevani, A.A., Kanani, Y., Khajeh, S., “A first-principles study of the adsorption behavior of CO on Al-and Ga-doped single-walled BN nanotubes”, Applied Surface Science, 270: 25–32, (2013). DOI: https://doi.org/10.1016/j.apsusc.2012.12.008
• [36] Hazrati, M.K., Hadipour, N.L., “Adsorption behavior of 5-fluorouracil on pristine, B-, Si-, and Al-doped C60 fullerenes: A first-principles study”, Physics Letters A, 380: 937–941, (2016). DOI: https://doi.org/10.1016/j.physleta.2016.01.020
• [37] Tomasi, J., Mennucci, B., Cammi, R., “Quantum Mechanical Continuum Solvation Models”, Chemical Reviews, 105: 2999–3094, (2005). DOI: https://doi.org/10.1021/cr9904009
• [38] Boys, S.F., Bernardi, F.D., “The calculation of small molecular interactions by the differences of separate total energies. Some procedures with reduced errors”, Molecular Physics, 19: 553–566, (1970). DOI: https://doi.org/10.1080/00268977000101561
• [39] Simon, S., Duran, M., Dannenberg, J., “How does basis set superposition error change the potential surfaces for hydrogen‐bonded dimers?”, The Journal of Chemical Physics, 105: 11024–11031, (1996). DOI: https://doi.org/10.1063/1.472902
• [40] Daboe, M., Parlak, C., Direm, A., Alver, Ö., Ramasami, P., “Interaction between escitalopram and ibuprofen or paracetamol: DFT and molecular docking on the drug–drug interactions”, Journal of Biomolecular Structure and Dynamics, 42(2): 672–686, (2024). DOI: 10.1080/07391102.2023.2195004