Naringenin-Based Oximes and Hydrazones: Synthesis, Molecular Docking with Bovine Serum Albumin and Drug-Likeness, Admet Profiling Studies

Yıl 2025, Cilt: 21 Sayı: 1, 66 - 74, 26.03.2025

Ferhat Melihcan Abay , Hafize Özcan , Ayşen Şuekinci Yılmaz , Ömer Zaim

https://doi.org/10.18466/cbayarfbe.1552978

Öz

Scientists are now increasingly interested in the flavonoid molecule naringenin due to the broad spectrum of biological roles it conducts. Oximes and hydrazones were created employing derivatives of the naringenin-active substances 7-piperidinethoxy and 7-morpholinethoxy to contribute to this research. The ability of the produced compounds to bind to BSA was determined by molecular docking and their potential as medications was assessed using various methods. Based on Lipinski's rule of five, none of the substances were hazardous or carcinogenic, and their blood-brain barrier crossing values were all within permissible limits.

Anahtar Kelimeler

BSA, Flavonoid, Hydrazones, Lipinski, Oximes

Etik Beyan

There are no ethical issues after the publication of this manuscript.

Destekleyen Kurum

Trakya University

Proje Numarası

TÜBAP 2018/232

Teşekkür

We gratefully acknowledge the financial support of the scientific research project commission of Trakya University (TÜBAP 2018/232).

Kaynakça

• [1]. Formica, J, Regelson, W. 1995. Review of the biology of quercetin and related bioflavonoids. Food and Chemical Toxicology; 33(12):1061-1080. https://doi.org/10.1016/0278-6915(95)00077-1.
• [2]. Cazarolli, LH, Zanatta, L, Alberton, EH, Bonorino, Figueiredo, MSR, Folador, P, Damazio, RG, et al. 2008. Flavonoids: prospective drug candidates. Mini Reviews in Medicinal Chemistry; 8(13):1429-1440. https://doi.org/10.2174/138955708786369564.
• [3]. Cushnie, TT, Lamb, AJ. 2011. Recent advances in understanding the antibacterial properties of flavonoids. International Journal of Antimicrobial Agents; 38(2):99-107. https://doi.org/10.1016/j.ijantimicag.2011.02.014.
• [4]. Miller, E, Schreier, P. Studies on flavonol degradation by peroxidase (donor: H2O2-oxidoreductase, EC 1.11. 1.7): Part 1—Kaempferol. Food Chemistry; 17(2):143-154. https://doi.org/10.1016/0308-8146(85)90083-4.
• [5]. Wiseman, H. 1996. Dietary influences on membrane function: importance in protection against oxidative damage and disease. The Journal of Nutritional Biochemistry; 7(1):2-15. https://doi.org/10.1016/0955-2863(95)00152-2.
• [6]. Hollman, P, Hertog, M, Katan, M. 1996. Role of dietary flavonoids in protection against cancer and coronary heart disease. Biochemical Society Transactions; 24:785-789. https://doi.org/10.1042/bst0240785.
• [7]. Zaim, Ö, Doğanlar, O, Zreigh, MM, Doğanlar, ZB, Özcan, H. 2018. Synthesis, Cancer‐Selective Antiproliferative and Apoptotic Effects of Some (±)‐Naringenin Cycloaminoethyl Derivatives. Chemistry & Biodiversity; 15(7):e1800016. https://doi.org/10.1002/cbdv.201800016
• [8]. Hodek, P, Trefil, P, Stiborová, M. 2002. Flavonoids-potent and versatile biologically active compounds interacting with cytochromes P450. Chemico-Biological Interactions, 139(1):1-21. https://doi.org/10.1016/S0009-2797(01)00285-X.
• [9]. Ahmadi, A, Hassandarvish, P, Lani, R, Yadollahi, P, Jokar, A, Bakar, SA, et al. 2016. Inhibition of chikungunya virus replication by hesperetin and naringenin. RSC Advances; 6(73):69421-69430. https://doi.org/10.1039/C6RA16640G.
• [10]. Denaro, M, Smeriglio, A, Trombetta, D. 2021. Antioxidant and anti-inflammatory activity of citrus flavanones mix and its stability after in vitro simulated digestion. Antioxidants; 10(2):140. https://doi.org/10.3390/antiox10020140.
• [11]. Babu, KS, Babu, TH, Srinivas, P, Kishore, KH, Murthy, U, Rao, JM. 2006. Synthesis and biological evaluation of novel C (7) modified chrysin analogues as antibacterial agents. Bioorganic & Medicinal Chemistry Letters; 16(1):221-2244. https://doi.org/10.1016/j.bmcl.2005.09.009
• [12]. Zaim, Ö, Doğanlar, O, Doğanlar, ZB, Özcan, H, Zreigh, MM, Kurtdere, K. 2022. Novel synthesis naringenin-benzyl piperazine derivatives prevent glioblastoma invasion by inhibiting the hypoxia-induced IL6/JAK2/STAT3 axis and activating caspase-dependent apoptosis. Bioorganic Chemistry; 129:106209. https://doi.org/10.1016/j.bioorg.2022.106209.
• [13]. Türkkan, B, Özyürek, M, Bener, M, Güçlü, K, Apak, R. 2012. Synthesis, characterization and antioxidant capacity of naringenin-oxime. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy; 85(1):235-240. https://doi.org/10.1016/j.saa.2011.09.066.
• [14]. Carter, DC, Ho, JX. 1994. Structure of serum albumin. Advances in Protein Chemistr; 45:153-203. https://doi.org/10.1016/S0065-3233(08)60640-3.
• [15]. Otagiri, M. 2005. A molecular functional study on the interactions of drugs with plasma proteins. Drug Metabolism and Pharmacokinetics, 20(5):309-323. https://doi.org/10.2133/dmpk.20.309.
• [16]. Zhang, G, Chen, X, Guo, J, Wang, J. 2009.Spectroscopic investigation of the interaction between chrysin and bovine serum albumin. Journal of Molecular Structure; 921(1-3):346-351. https://doi.org/10.1016/j.molstruc.2009.01.036.
• [17]. Trott, O, Olson, AJ. 2010. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry; 31(2):455-461. https://doi.org/10.1002/jcc.21334.
• [18]. Masand, VH, Rastija, V. 2017. PyDescriptor: A new PyMOL plugin for calculating thousands of easily understandable molecular descriptors. Chemometrics and Intelligent Laboratory Systems 169:12-18. https://doi.org/10.1016/j.chemolab.2017.08.003.
• [19]. Studio D. 2008. “Discovery studio” Accelrys [21]. 2008. https://discover.3ds.com/discovery-studio-visualizer-download.
• [20]. Lipinski, CA. 2004. Lead-and drug-like compounds: the rule-of-five revolution. Drug Discovery Today: Technologies; 1(4):337-341. https://doi.org/10.1016/j.ddtec.2004.11.007.
• [21]. Job, P. 1928. Job’s plot analyses for the 2-CG and 3-CG complexes were consistent with 1: 1 stoichiometry. Annalen der Chemie; 9:113-34.
• [22]. Latif, A. D., Gonda, T., Vágvölgyi, M., Kúsz, N., Kulmány, Á., Ocsovszki, I., Hunyadi, A. 2019. Synthesis and in vitro antitumor activity of naringenin oxime and oxime ether derivatives. International Journal of Molecular Sciences; 20(9), 2184. https://doi.org/10.3390/ijms20092184
• [23]. Ferreira, R. J., Gajdács, M., Kincses, A., Spengler, G., Dos Santos, D. J., Ferreira, M. J. U. 2020. Nitrogen-containing naringenin derivatives for reversing multidrug resistance in cancer. Bioorganic & Medicinal Chemistry, 28(23), 115798. https://doi.org/10.1016/j.bmc.2020.115798
• [24]. Yılmaz, AŞ, Uluçam, G. 2023. Novel N-benzyl-2-oxo-1, 2-dihydrofuro [3, 4-d] pyrimidine-3 (4H)-carboxamide as anticancer agent: Synthesis, drug-likeness, ADMET profile, DFT and molecular modelling against EGFR target. Heliyon; e12948. https://doi.org/10.1016/j.heliyon.2023.e12948.
• [25]. Hu, Y. J., Wang, Y., Ou-Yang, Y., Zhou, J., & Liu, Y. 2010. Characterize the interaction between naringenin and bovine serum albumin using spectroscopic approach. Journal of Luminescence, 130(8), 1394-1399. https://doi.org/10.1016/j.jlumin.2010.02.053
• [26]. Liu, J., Yang, Z., Cheng, Y., Wu, Q., He, Y., Li, Q., & Cao, X. 2020. Eriodictyol and naringenin inhibit the formation of AGEs: An in vitro and molecular interaction study. Journal of Molecular Recognition, 33(1), e2814. https://doi.org/10.1002/jmr.2814
• [27]. Daina, A, Michielin, O, Zoete, V. 2017. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports; 7(1):42717. https://www.nature.com/articles/srep42717.