The Licochalcone Compound A: Theoretical Studies Applied with DFT Method and Molecular Docking Simulations

Abstract

Alzheimer's disease (AD) is a health problem that is becoming widespread in the medical sector all over the world. Due to the limited treatment of AD, new clinical candidates are sought. Given the multifactorial nature of AD, an approach targeting the number of regulatory proteins that play a role in the development of the disease is an effective approach. For this reason, interest in different treatment methods has naturally increased in recent years. Medicinal plants and their extracts have been used extensively for the healing of many wounds for years, both professionally and in alternative medicine. Among these natural compounds, these compounds have been of particular interest due to their pharmacological properties such as antioxidants and free radical scavengers. In this study, the molecular geometry, molecular electrostatic potential, and nonlinear optical studies of the Licochalcone A molecule were elucidated by using the density functional theory (DFT) method. In addition, charge transfer within the molecule, HOMO-LUMO energy calculations and Mulliken atomic charge distributions were studied and the results were interpreted with visuals. This analysis also provides drug candidate information about the compound with ligand-receptor binding modes through molecular docking studies.

Keywords

• Licochalcone A
• TD-DFT
• HOMO-LUMO
• Molecular docking

Licochalcone Bileşiği A: DFT Yöntemi ve Moleküler Yerleştirme Simülasyonları ile Uygulanan Teorik Çalışmalar

Abstract

Alzheimer hastalığı (AD), tıbbi sektörde tüm dünyada yaygınlaşan bir sağlık sorunudur. AD'nin sınırlı tedavisi nedeniyle yeni klinik aday aranıyor. AD'nin çok faktörlü yapısı göz önüne alındığında, hastalığın gelişiminde rol oynayan düzenleyici proteinlerin sayısını hedefleyen bir yaklaşım etkili bir yaklaşımdır. Bu nedenle farklı tedavi yöntemlerine olan ilgi de son yıllarda doğal olarak artmıştır. Şifalı bitkiler ve özleri, hem profesyonel olsun hem de alternatif tıp ile yıllardır bir çok yaraların iyileştirilmesinde çokça kullanılmıştır. Bu doğal bileşikler arasında antioksidanlar ve serbest radikal süpürücüler gibi farmakolojik özellikleri sebebiyle bu birleşiklerle özel olarak ilgilenilmiştir. Bu çalışmada Licochalcone A molekülünün yoğunluk fonksiyonel teorisi (DFT) metodu kullanılarak optimize edilmiş moleküler geometri, moleküler elektrostatik potansiyel ve doğrusal olmayan optik çalışmalar hakkında molekülün yapısı aydınlatılmıştır. Ayrıca molekül içindeki yük transferi, HOMO-LUMO enerji hesaplamaları ve Mulliken atomik yük dağılımları incelendi ve sonuçlar görsellerle yorumlandı. Bu analiz ayrıca moleküler yerleştirme çalışmaları yoluyla ligand-reseptör bağlanma modlarına sahip bileşik hakkında ilaç adayı bilgisi de sağlar.

Keywords

• Licochalcone A
• TD-DFT
• HOMO-LUMO
• Moleküler yerleştirme

References

1. [1] Ivosevic, M., et al. 2024 Detection and management of suspected infections in people with dementia – a scoping review of current practices. Ageing Research Reviews, 102520.
2. [2] Connor, J. 2024. Diagnosis and management of dementia in older people. Medicine, 49(1), 22-25.
3. [3] Amin, J. and McCausland, B. 2024. Dementia. Medicine, 52(8), 518-521.
4. [4] Moody, E., et al. 2024. Nursing interventions to improve care of people living with dementia in hospital: A mixed methods systematic review. International Journal of Nursing Studies, 158, 104838.
5. [5] Carrarini, C., et al. 2024. Neuropsychological and electrophysiological measurements for diagnosis and prediction of dementia: a review on Machine Learning approach. Ageing Research Reviews, 100, 102417.
6. [6] Marsool, M.D.M., et al. 2023. Newer modalities in the management of Alzheimer's dementia along with the role of aducanumab and lecanemab in the treatment of its refractory cases. Disease-a-Month, 69(5), 101547.
7. [7] Ding, H., et al. 2022. Cryptotanshinone against vascular dementia through inhibition of Aβ aggregation and inflammatory responses in cerebrovascular endothelial cells. Arabian Journal of Chemistry, 15(12), 104328.
8. [8] Steiner, H., et al. 2018. Making the final cut: pathogenic amyloid-β peptide generation by γ-secretase. Cell Stress, 2(11), 292.

9. [9] Schultz, S.A., et al. 2024. γ-Secretase activity, clinical features, and biomarkers of autosomal dominant Alzheimer's disease: cross-sectional and longitudinal analysis of the Dominantly Inherited Alzheimer Network observational study (DIAN-OBS). The Lancet Neurology, 23(9), 913-924.
10. [10] Torres, P.H., et al. 2019. Key topics in molecular docking for drug design. International journal of molecular sciences, 20(18), 4574.
11. [11] Ries, M. and Sastre M. 2016. Mechanisms of Aβ clearance and degradation by glial cells. Frontiers in aging neuroscience, 8, 160.
12. [12] Xu, X. 2009. γ-Secretase catalyzes sequential cleavages of the AβPP transmembrane domain. Journal of Alzheimer's Disease, 16(2), 211-224.
13. [13] Checler, F., et al. 2021. Is γ-secretase a beneficial inactivating enzyme of the toxic APP C-terminal fragment C99? Journal of Biological Chemistry, 296.
14. [14] Genç, M., et al. 2022. Synthesis, structural characterization and anticancer activity of 3-(3, 5-dinitrobenzoyl)-1 H-imidazolidine-2-thione. Indian Journal of Chemistry (IJC), 61(2), 201-209.
15. [15] Genç, M. 2019. Solvatochromic analysis and DFT computational study of N-(hexyl)-N-(5-(3-hydroxynaphthyl-2-yl)-1, 3, 4-oxadiazol-2-yl) amine. Applied Physics A, 125(6), 1-14.
16. [16] Frisch, M., et al. 2009. Gaussian Inc. Wallingford Ct, 2.
17. [17] Selvam, C., et al. 2005. Design, synthesis, biological evaluation and molecular docking of curcumin analogues as antioxidant, cyclooxygenase inhibitory and anti-inflammatory agents. Bioorganic & medicinal chemistry letters, 15(7), 1793-1797.
18. [18] Hanessian, S., et al. 2010. Structure-based design and synthesis of novel P2/P3 modified, non-peptidic beta-secretase (BACE-1) inhibitors. Bioorg Med Chem Lett, 20(6), 1924-7.
19. [19] Yang, G., et al. 2021. Structural basis of γ-secretase inhibition and modulation by small molecule drugs. Cell, 184(2), 521-533.e14.
20. [20] Adejoro, I.A. and Oyeneyin, O. 2013. Characterization of a novel polymeric Zinc (II) complex containing the anti-malarial Quinine as ligand: A Theoretical Approach (Semi-empirical and DFT methods). American Journal of Scientific and Industrial Research, 4, 111-122.
21. [21] Yİldİko, Ü., et al. 2021. Investigation of novel diethanolamine dithiocarbamate agent for RAFT polymerization: DFT computational study of the oligomer molecules. Bulletin of Materials Science, 44(3), 1-13.
22. [22] Şen, B., et al. 2016. Synthesis, structural characterization, and DFT calculations of 3-buthyl-4-(3-methyl-3-mesitylcyclobut-1-yl)-1, 3-thiazole-2 (3H)-thione. Crystallography Reports, 61(2), 243-248.
23. [23] Pandey, P., et al. 2023. A combined experimental and computational chiroptical approach to establish the biosynthesis and absolute configuration of licochalcone L. Phytochemistry, 212, 113732.
24. [24] Ani, F.E., et al. 2021. Crystal, spectroscopic and quantum mechanics studies of Schiff bases derived from 4-nitrocinnamaldehyde. Scientific Reports, 11(1), 8151.
25. [25] Karagoz Genç, Z., et al. 2021. The novel tetrahydropyrimidine derivative as inhibitor of SARS CoV-2: synthesis, modeling and molecular docking analysis. Journal of Biomolecular Structure and Dynamics, 10045-10056.
26. [26] Şenol, Z.M., et al. 2022. Epichlorohydrin and tripolyphosphate-crosslinked chitosan–kaolin composite for Auramine O dye removal from aqueous solutions: Experimental study and DFT calculations. International Journal of Biological Macromolecules, 199, 318-330.
27. [27] Karabulut, B. and Kirilmiş C. 2020. 5-((4-brom-2-klorfenoksi) metil) oksazolidin-2-on ve 5-((2-brom-4-klorfenoksi) metil) oksazolidin-2-on bileşiklerinin Sentezi ve Teorik Hesaplamaları. Bitlis Eren Üniversitesi Fen Bilimleri Dergisi, 9(2), 500-511.
28. [28] Karabıyık, H., Kırılmış, C. and Karabıyık H. 2017. Geometry dependence of electron donating or accepting abilities of amine groups in 4, 4′-disulfanediylbis (methylene) dithiazol-2-amine: Pyramidal versus planar. Journal of Molecular Structure, 1141, 650-659.
29. [29] Yildiko, U. and Tanriverdi, A.A. 2022. A novel sulfonated aromatic polyimide synthesis and characterization: Energy calculations, QTAIM simulation study of the hydrated structure of one unit. Bulletin of the Korean Chemical Society, 43(6), 822-835.
30. [30] Huang, Y., et al. 2016. Evaluating frontier orbital energy and HOMO/LUMO gap with descriptors from density functional reactivity theory. Journal of Molecular Modeling, 23(1), 3.
31. [31] Benaissa, M., et al. 2024. Periodic and non-periodic DFT studies of an organic semiconductor material: Structural, electronic, optical, and vibrational properties of ninhydrin. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 307, 123636.
32. [32] Nelson, R., et al. 2020. LOBSTER: Local orbital projections, atomic charges, and chemical‐bonding analysis from projector‐augmented‐wave‐based density‐functional theory. Journal of Computational Chemistry, 41(21), 1931-1940.
33. [33] Martin, F. and Zipse, H. 2005. Charge distribution in the water molecule—A comparison of methods. Journal of Computational Chemistry, 26(1), 97-105.
34. [34] Shree, P., et al. 2022. Targeting COVID-19 (SARS-CoV-2) main protease through active phytochemicals of ayurvedic medicinal plants–Withania somnifera (Ashwagandha), Tinospora cordifolia (Giloy) and Ocimum sanctum (Tulsi)–a molecular docking study. Journal of Biomolecular Structure and Dynamics, 40(1), 190-203.
35. [35] Yildiko, Ü., et al. 2021. Synthesis, enzymes inhibitory properties and characterization of 2-(bis (4-aminophenyl) methyl) butan-1-ol compound: Quantum simulations, and in-silico molecular docking studies. Journal of the Indian Chemical Society, 98(11), 100206.
36. [36] Liang, L., et al. 2022. Characterization and molecular docking study of taste peptides from chicken soup by sensory analysis combined with nano-LC-Q-TOF-MS/MS. Food Chemistry, 383, 132455.
37. [37] TEKEŞ, A.T., et al. 2021. Insilico Molecular Docking Studies of THBF Compound: TD-DFT Simulations and Drug Design. Journal of the Institute of Science and Technology, 11(4), 2955-2966.
38. [38] Abdullah et al. 2024. Selenium-substituted conjugated small molecule: Synthesis, spectroscopic, computational studies, antioxidant activity, and molecular docking. Journal of Molecular Structure, 1304, 137694.
39. [39] El-Shalakany, H.H., Ramadan, R.M. and Sayed, M.A. 2024. New bivalent metal chelates based on an NO-donor Schiff base ligand: synthesis, structural characterization, DFT simulation, biological evaluation, and molecular docking analysis. Inorganic Chemistry Communications, 159, 111826.
40. [40] Swasticharan, L., et al. 2024. A combined metagenome and disease enrichment analysis of nitrosamines present in smokeless tobacco, wiz using molecular docking and functional annotation approach. Gene Reports, 36, 101929.