A Heterocyclic Compound Hispidulin: Theoretical Investigation by DFT/TD-DFT Methods and Molecular Docking Studies

Yıl 2022, , 515 - 522, 20.12.2022

Ahmet Çağrı Ata , Aslıhan Aycan Tanrıverdi , Ümit Yıldıko , İsmail Çakmak

https://doi.org/10.19113/sdufenbed.1126132

Cited By: 1

Öz

Flavonoids are polyphenolic plant secondary metabolites with biological properties including Alzheimer's disease (AD) inhibition activities. Numerous studies have been conducted on naturally occurring flavonoids modified to obtain effective drugs for the management of AD. In this study, DFT/B3PW91, TD-DFT/B3LYP methods of target molecule hispidulin 4′,5,7-Trihydroxy-6-Methoxyflavone (THMF) and LANL2DZ (d,p), 6-311G (d,p) basic HOMO-LUMO energy calculations, optimized molecular geometry, molecular electrostatic potential surface (MEPS), non-linear optics (NLO), charge transfer within the molecule and mulliken atomic charges structure were determined and the results were displayed. Moreover the identification of the mechanism of action of the tested compound based on the structure-activity relationship with the molecular docking process is to provide important information to be considered for further research, and thus to design new, more efficient and selective systems.

Anahtar Kelimeler

Hispidulin, DFT, TD-DFT, Molecular Docking

Bir Heterosiklik Bileşik Hispidulin: DFT/TD-DFT Metotları ile Teorik Olarak İncelenmesi ve Moleküler Yerleştirme Çalışmaları

Öz

Flavonoidler, Alzheimer hastalığı (AD) inhibisyon aktiviteleri de dahil olmak üzere biyolojik özelliklere sahip polifenolik bitki ikincil metabolitleridir. AH yönetimi için etkili ilaçlar elde etmek için modifiye edilmiş doğal olarak oluşan flavonoidler üzerinde çok sayıda araştırma yapılmıştır. Bu çalışmada, hedef molekül hispidulin 4′,5,7-Trihidroksi-6-Metoksiflavon (THMF)’in DFT/B3PW91, TD-DFT/B3LYP yöntemleri ve LANL2DZ (d,p), 6-311G (d,p) temel setleri kullanılarak HOMO-LUMO enerji hesaplamaları, optimize edilmiş moleküler geometri, moleküler elektrostatik potansiyel yüzey (MEPS), doğrusal olmayan optik (NLO), molekül içindeki yük transferi ve mulliken atomik yükleri yapısı belirlendi ve sonuçlar görüntülendi. Ayrıca, moleküler yerleştirme işlemiyle yapı-aktivite ilişkisine dayalı olarak test edilen bileşiğin etki mekanizmasının tanımlanması, daha sonraki araştırmalar için dikkate alınması gereken önemli bilgiler sağlamak ve bu sayede yeni, daha verimli ve seçici sistemleri tasarlamaktır.

Anahtar Kelimeler

Hispidulin, DFT, TD-DFT, Moleküler Yerleştirme

Kaynakça

• [1] Brookmeyer, R., Johnson, E., Ziegler-Graham, K., Arrighi, H. M. 2007. Forecasting the global burden of Alzheimer’s disease. Alzheimer's & dementia, 3(3), 186-191.
• [2] Karantzoulis, S., Galvin, J. E. 2011. Distinguishing Alzheimer’s disease from other major forms of dementia. Expert review of neurotherapeutics, 11(11), 1579-1591.
• [3] Ozturk, O., Farouk, F. M., Ooi, L., Law, C. S. W., Muhammed, M. T., Aki-Yalcin, E., Yeong, K. Y. 2022. Synthesis of novel carboxamide-and carbohydrazide-benzimidazoles as selective butyrylcholinesterase inhibitors. Molecular Diversity, 26(5), 2863-2876.
• [4] Phosrithong, N., Samee, W., Nunthanavanit, P., Ungwitayatorn, J. 2012. In vitro antioxidant activity study of novel chromone derivatives. Chemical Biology & Drug Design, 79(6), 981-989.
• [5] Jalili-Baleh, L., Babaei, E., Abdpour, S., Bukhari, S. N. A., Foroumadi, A., Ramazani, A., Khoobi, M. 2018. A review on flavonoid-based scaffolds as multi-target-directed ligands (MTDLs) for Alzheimer's disease. European journal of medicinal chemistry, 152, 570-589.
• [6] Berk, Ş., Kaya, S., Akkol, E. K., Bardakçı, H. 2022. A comprehensive and current review on the role of flavonoids in lung cancer: experimental and theoretical approaches. Phytomedicine, 153938.
• [7] Zagal, J. H., Griveau, S,. Silva, J. F., Nyokong, T., Bedioui, F. 2010. Metallophthalocyanine-based molecular materials as catalysts for electrochemical reactions. Coordination Chemistry Reviews, 254(23-24), 2755-2791.
• [8] Urbani, M., de la Torre, G., Nazeeruddin, M. K., Torres, T. 2019. Phthalocyanines and porphyrinoid analogues as hole-and electron-transporting materials for perovskite solar cells. Chemical Society Reviews, 48(10), 2738-2766.
• [9] Cabir, B., Yildiko, U., Ağırtaş, M. S., Horoz, S. 2020. Computational DFT calculations, photovoltaic properties and synthesis of (2R, 3S)-2, 3, 4-trihydroxybutoxy substituted phthalocyanines. Inorganic and Nano-Metal Chemistry, 50(9), 816-827.
• [10] Lo, P-C., Rodríguez-Morgade, M. S., Pandey, R. K., Ng, D. K., Torres, T., Dumoulin, F. 2020. The unique features and promises of phthalocyanines as advanced photosensitisers for photodynamic therapy of cancer. Chemical Society Reviews, 49(4), 1041-1056.
• [11] Yildiko, Ü., Ata, A. Ç., Tanriverdi A. A., Çakmak, İ. 2021. Investigation of novel diethanolamine dithiocarbamate agent for RAFT polymerization: DFT computational study of the oligomer molecules. Bulletin of Materials Science, 44(3), 186.
• [12] Frisch, M. 2019. Gaussian09. http://www. gaussian.com (Erişim Tarihi: 05.01.2021).
• [13] Dennington, R., Keith, T. A., Millam, J. M. 2016. GaussView, version 6.0.16. Semichem Inc., Shawnee Mission, KS.
• [14] Madhavi Sastry, G., Adzhigirey, M., Day, T., Annabhimoju, R., Sherman, W. 2013. Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments. Journal of Computer-Aided Molecular Design, 27(3), 221-234.
• [15] Brodney, M. A., Barreiro, G., Ogilvie, K., Hajos-Korcsok, E., Murray, J., Vajdos, F., Ambroise, C., Christoffersen, C., Fisher, K., Lanyon, L., Liu, J., Nolan, C. E., Withka, J. M., Borzilleri, K. A., Efremov, I., Oborski, C. E., Alison Varghese, A., O’Neill, B. T. 2012. Spirocyclic sulfamides as β-secretase 1 (BACE-1) inhibitors for the treatment of Alzheimer’s disease: Utilization of structure based drug design, watermap, and CNS penetration studies to identify centrally efficacious inhibitors. Journal of Medicinal Chemistry, 55(21), 9224-9239.
• [16] Kupski, O., Funk, L. M., Sautner, V., Seifert, F., Worbs, B., Ramsbeck, D., Meyer, F., Diederichsen, U., Buchholz, M., Schilling, S., Demuth, H. U., Tittmann, K. 2020. Hydrazides are potent transition-state analogues for glutaminyl cyclase implicated in the pathogenesis of Alzheimer’s disease. Biochemistry, 59(28), 2585-2591.
• [17] BIOVIA Discovery Studio D. SYSTÈMES BIOVIA Corporate Europe, BIOVIA 334 Cambridge Science Park Cambridge. 2016 http://accelrys.com/products/collaborative-science/biovia-discovery-studio/ (Erişim Tarihi: 05.01.2021).
• [18] Erol, M., Çelik, İ., Kuyucuklu, G. 2021. Bazı yeni 2, 5-disübstitüe benzoksazol türevlerinin sentezi, antimikrobiyal aktivite, moleküler doking ve dft çalışmaları. Avrupa Bilim ve Teknoloji Dergisi, 27, 605-614.
• [19] Üstün, E., Şahin, N. 2021. Molecular docking and dft analysis of methallyl substituted n-heterocyclic carbene salts for potential anticancer activity. Ordu Üniversitesi Bilim ve Teknoloji Dergisi, 11(2), 186-192.
• [20] Bhuvaneswari, R., Bharathi, M. D., Anbalagan, G., Chakkaravarthi, G., Murugesan, K. S. 2018. Molecular structure, vibrational spectroscopic (FT-IR, FT-Raman), NBO, HOMO and LUMO analysis of morpholinium oxalate by density functional method. Journal of Molecular Structure, 1173, 188-195.
• [21] Mary, Y. S., Yalcin, G., Mary, Y. S., Resmi, K. S., Thomas, R., Önkol, T., Kasap, E. N., Yildiz, I. 2020. Spectroscopic, quantum mechanical studies, ligand protein interactions and photovoltaic efficiency modeling of some bioactive benzothiazolinone acetamide analogs. Chemical Papers, 74(6), 1957-1964.
• [22] Altun, K., Yıldıko, Ü., Tanrıverdi, A. A., Çakmak, İ. Structural and spectral properties of 4-(4-(1-(4-Hydroxyphenyl)-1-phenylethyl) phenoxy) phthalonitrile: Analysis by TD-DFT method, ADME analysis and docking studies. International Journal of Chemistry and Technology, 5(2), 147-155.
• [23] Bernetti, M., Cavalli, A., Mollica, L. 2017. Protein–ligand (un) binding kinetics as a new paradigm for drug discovery at the crossroad between experiments and modelling. MedChemComm, 8(3), 534-550.
• [24] Yildiko, Ü., Türkan, F., Tanriverdi, A. A., Ata, A. C., Atalar, M. N., Cakmak, İ. 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.
• [25] Kupski, O., Funk, L. M., Sautner, V., Seifert, F., Worbs, B., Ramsbeck, D., Tittmann, K. 2020. Hydrazides are potent transition-state analogues for glutaminyl cyclase implicated in the pathogenesis of Alzheimer’s disease. Biochemistry, 59(28), 2585-2591.
• [26] Brodney, M. A., Barreiro, G., Ogilvie, K., Hajos-Korcsok, E., Murray, J., Vajdos, F., O’Neill, B. T. 2012. Spirocyclic sulfamides as β-secretase 1 (BACE-1) inhibitors for the treatment of Alzheimer’s disease: Utilization of structure based drug design, watermap, and CNS penetration studies to identify centrally efficacious inhibitors. Journal of medicinal chemistry, 55(21), 9224-9239.