İstanbul Journal of Pharmacy

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DOI :10.26650/IstanbulJPharm.2025.1545031   IUP :10.26650/IstanbulJPharm.2025.1545031    Tam Metin (PDF)

In silico studies concerning the cytotoxic potential and the inhibition of cytochrome P450 of some bioactive compounds present in Asphodeline lutea root extracts

Irina Lazarova, Emilio Mateev, Gökhan Zengin

Background and Aims: The roots of Asphodeline lutea are traditionally consumed in the diet of people from Mediterranean countries. The methanol root extracts of A. lutea have been proven to possess cytotoxic activity against the MCF-7 and MCF-10A cell lines. The goal of our investigation was to determine the physicochemical and pharmacokinetic properties, possible inhibition against CYP450 isoenzymes, and probable cytotoxic effect of some bioactive components isolated from A. lutea roots using in silico methods.

Methods: The Absorption, distribution, metabolism, and excretion (ADME) profiles were determined using the freely available SwissADME server. To increase the robustness of the SwissADME results, further calculations with the QikProp module in Maestro were carried out. The docking studies were carried out with Glide. The Induced-fit docking (IFD) and Molecular Mechanics-Generalized Born Surface Area (MM/ GBSA) modules in Maestro were applied for recalculations. The anticancer activities were predicted by the online server CLC-Pred.

Results: The in silico ADME studies identified chrysophanol and helminthosporin as suitable for future evaluations considering their optimal pharmacokinetic profiles. The former compounds adhere to all of Lipinski’s rule of five for drug likeness. The docking studies identified helminthosporin as a potential inhibitor of CYP1A2 and a weak CYP3A4 inhibitor. Chrysophanol, helminthosporin, asphodelin and 10, 7'-bichrysophanol are expected to manifest a strong cytotoxic effect against A2780cisR cell line. They exerted a strong to modest cytotoxic effect against HOP-18, RCC4 and M19-MEL cell lines. 1,5,8-trihydroxy-3- methylanthraquinone exhibited modest action against GIST430 cell line, while 10, 7'-bichrysophanol had moderate activity against A2780 and SW1990 cell lines.

Conclusion: Our findings justify the future in vitro and in vivo studies of A. lutea plant extracts as potential anticancer agents. 

Anahtar Kelimeler: Asphodeline lutea, Cytotoxicity, In silico, Molecular docking

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Referanslar

  • Angelov, B., Mateev,E., Georgieva, M., Tzankova, V., & Kondeva-Burdina, M. (2022). İn vitre effects and in silice analYsis of newlY sYnthetized pYrrole derivatives on the activitY of different isoforms of CYtochrome P450: CYP1A2, CYP2D6 and CYP3A4. Pharmacia, 69 (4), 1013-1017. https://doi.org/10.3897/pharmacia. 69.e96626 google scholar
  • Appiah-Opong, R., de Esch, I., Commandeur, J. N. M., Andarini, M., & Vermeulen, Nico P. E. (2008). Structure-activitY relationships for the inhibition of recom-binant human cYtochromes P450 bY curcumin analogues. Eurepean Jeurnal ef Medicinal Chemistry, 43(8), 1621-1631. https://www.sciencedirect.com/science/ article/pii/S0223523407004291 google scholar
  • Atanasov, A.G., Zotchev, S.B., Dirsch, V.M., Orhan, I. E., Banach, M., Rollinger, J. M., Barreca, D., Weckwerth, W., Bauer, R., BaYer, E. A., Majeed, M., BishaYee, A., Bochkov, V., Bonn, G. K., BraidY, N., Bucar, F., Cifuentes, A., D’Onofrio, G., Bodkin, M.,....., & Supuran, C. T. (2021). Natural products in drug discoveıy: advances and opportunities. Nature Reviews Drug Discoveıy, 20, 200-216. https://doi.org/10.1038/s41573-020-00114-z google scholar
  • Bonomo, S., Jprgensen, F.S., & Olsen L. (2017). Dissecting the CYtochrome P450 1A2-and 3A4-mediated metabolism of aflatoxin B1 in ligand and protein contri-butions. Chemistry - A European Journal, 23(12), 2884-2893. https://doi.org/10. 1002/chem.201605094 google scholar
  • 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, 42717. https://doi.org/10.3390/10.1038/ srep42717 google scholar
  • Dulsat, J., Lopez-Nieto, B., Estrada-Tejedor, R., & Borrell, J. I. (2023). Evaluation of free online ADMET tools for academic or small biotech environments. Molecules (Basel, Switzerland), 28(2), 776. https://doi.org/10.3390/molecules28020776 google scholar
  • Durân-lturbide, N. A., Dıaz-Eufracio, B. I., & Medina-Franco, J. L. (2020). İn silice ADME/ Tox profiling of natural products: a focus on BIOFACQUIM. ACS Omega, 5(26), 16076-16084. https://doi.org/10.1021/acsomega.0c01581 google scholar
  • Ekroos, M., & Sjögren, T. (2006). Structural basis for ligand promiscuitY in cy-tochrome P450 3A4. Proceedings of the National Academy of Sciences of the United States of America, 103(37), 13682-13687. https://doi.org/10.1073/pnas. 0603236103 google scholar
  • Kim, D-H., Kim, K-H., Kim, D., Jung , H-Ch., Pan, J-G., Chi, Y-T., Ahn, T., & Yun Ch-H. (2010). Oxidation of human cytochrome P450 1A2 substrates by Bacillus megaterium cYtochrome P450 BM3. Journal of Molecular Catalysis B: Enzymatic, 63, 179-187. https://doi.org/10.1016/j.molcatb.2010.01.017. google scholar
  • Kivistö, KT., Kroemer, HK., & Eichelbaum M. (1995). The role of human cytochrome P450 enzymes in the metabolism of anticancer agents: implications for drug inter-actions. British Journal of Clinical Pharmacology, 40(6), 523-30. doi: 10.1111/ j.1365-2125.1995.tb05796.x. google scholar
  • Lagunin, A. A., Dubovskaja, V. I., Rudik, A. V., Pogodin, P. V., Druzhilovskiy, D. S., Glorio-zova, T. A., Filimonov, D. A., SastrY, N. G., & Poroikov, V. V. (2018). CLC-Pred: A freely available web-service for in silico prediction of human cell line cYtotoxicitY for drug-like compounds. PLOS one, 13(1), e0191838. https://doi.org/10.1371/ journal.pone.0191838 google scholar
  • Lahlou, M. (2013). The success of natural products in drug discoverY. Pharmacology & Pharmacy, 4, 17-31. https://doi.org/10.4236/pp.2013.43A003. google scholar
  • Lazarova, I., Zengin, G., Aktumsek, A., Gevrenova, R., CeYlan, R., & UYsal, S. (2014). HPLC-DAD analYsis of phenolic compounds and antioxidant properties of As-phodeline lutea roots from Bulgaria and TurkeY. İndustrial Crops and Products, 61, 438-441. https://doi.org/10.1016/j.indcrop.2014.07.044. google scholar
  • Lazarova, I., Zengin, G., Bender, O., Zheleva-Dimitrova, D., UYsal, S., CeYlan, R., Gevren-ova, R., Aktumsek, A., Acar, M., & Gunduz, M. (2015). A comparative studY of Bulgarian and Turkish Asphodeline lutea root extracts: HPLC-UV profiles, enzYme inhibitorY potentials and anti-proliferative activities against MCF-7 and MCF-10A cell lines. Journal of Functional Foods, 15, 254-263. https://doi. org/10.1016/j.jff.2015.03.032 google scholar
  • Liu, R., Lyu, X., Batt, S. M., Hsu, M. H., Harbut, M. B., Vilcheze, C., Cheng, B., AjaYİ, K., Yang, B., Yang, Y., Guo, H., Lin, C., Gan, F., Wang, C., Franzblau, S. G., Jacobs, W. R., Jr, Besra, G. S., Johnson, E. F., Petrassi, M., Chatterjee, A. K., . Wang, F. (2017). Determinants of the Inhibition of DprE1 and CYP2C9 bY Antitubercular Thiophenes. Angewandte Chemie (İnternational ed, in English), 56(42), 1301113015. https://doi.org/10.1002/anie.201707324 google scholar
  • Majumder, R., Kanta Das, Ch., & Mandal M. (2019). Lead bioactive compounds of Aloe vera as potential anticancer agent. Pharmacological Research, 148, 104416. https://doi.org/10.1016/j.phrs.2019.104416 google scholar
  • Malik, M. S., Alsantali, R. I., Jassas, R. S., Alsimaree, A. A., SYed, R., Alsharif, M. A., Kalpana, K., Morad, M., Althagafi, I. I., & Ahmed, S. A. (2021). JourneY of anthraquinones as anticancer agents - a sYstematic review of recent literature. RSC Advances, 11(57), 35806-35827. https://doi.org/10.1039/d1ra05686g google scholar
  • Mateev, E., Balkanska-Mitkova, A., Peikova, L., Dimitrova, M., & Kondeva-Burdina, M. (2022). İn vitro and in silico inhibition performance of choline against CYP1A2, CYP2D6 and CYP3A4. Biotechnology & Biotechnological Equipment, 36(1), 925932. https://doi.org/10.1080/13102818.2022.2144452 google scholar
  • Marechal, J.D., Yu, J., Brown, S., Kapelioukh, I., Rankin, E.M., Wolf, C.R., & Sutcliffe, M.J. (2006). İn silico and in vitro screening for inhibition of cYtochrome p450 cYp3a4 bY comedications commonlY used bY patients with cancer. Drug Metabolism and Disposition, 34(4), 534-538. https://doi.org/10.1124/dmd.105.007625. google scholar
  • Pajouhesh, H., & Lenz, GR. (2005). Medicinal chemical properties of successful cen-tral nervous sYstem drugs. NeuroRx,, 2(4), 541-553. https://link.springer.com/ article/10.1602/neurorx.2.4.541 google scholar
  • Ridhwan, M.J.M., Bakar, S.I A., Latip, N.Ab., Ghani, N. Ab. I., & Nor Hadiani, A. (2022). Comprehensive analYsis of human CYP3A4 crYstal structures as a potential tool for molecular docking-based site of metabolism and enzYme inhibition studies. Journal of Computational Biophysics and Chemistry, 21(3), 259-285. https://doi.org/10.1142/S2737416522300012 google scholar
  • Sansen, S., Yano, J. K., ReYnald, R. L., Schoch, G. A., Griffin, K. J., Stout, C. D., & Johnson, E. F. (2007). Adaptations for the oxidation of polYcYclic aromatic hYdrocarbons exhibited bY the structure of human P450 1A2. The Journal of Biological Chemistry, 282(19), 14348-14355. https://doi.org/10.1074/jbc.M611692200 google scholar
  • Sun, D., Gao, W., Hu, H., & Zhou, S. (2022). WhY 90% of clinical drug development fails and how to improve it?. Acta Pharmaceutica Sinica, 12(7), 3049-3062. https:// doi.org/10.1016/j.apsb.2022.02.002 google scholar
  • Tikhomirov, A. S., Shtil, A. A., & Shchekotikhin, A. E. (2018). Advances in the Discovery of Anthraquinone-Based Anticancer Agents. Recent Patents on Anti-cancer Drug Discovery, 13(2), 159-183. https://doi.org/10.2174/1574892813666171206123114 google scholar
  • Tilaoui, M., Mouse., H. A., & ZYad, A. (2021). Update and new insights on future cancer drug candidates from plant-based alkaloids. Frontiers in Pharmacology, 12, 1-19. https://doi.org/10.3389/fphar.2021.719694 google scholar
  • Todorova, G., Lazarova, I., Mikhova, B., & Kostova, I. (2010). Anthraquinone, naphtha-lene and naphthaquinone components of Asphodeline lutea. Chemistry of Natural Compounds,, 46(2), 322-323. https://doi.org/10.1007/s10600-010-9604-7 google scholar
  • Wang, E., Sun, H., Wang, J., Wang, Z., Liu, H., Zhang, J. Z. H., & Hou T. (2019). End-point binding free energy calculation with MM/PBSA and MM/GBSA: strategies and applications in drug design. Chemical Reviews,, 119(16), 9478-9508. https://doi. org/ 10.1021/acs.chemrev.9b00055. google scholar
  • YuenYongsawad, S., Bunluepuech, K.,Wattanapiromsakul, C., & Tewtrakul, S. (2014). Anti-cancer activitY of compounds from Cassia garrettiana heartwood. Songk-lanakarin Journal of Science and Technology, 36, 189-194. https://www. thaiscience.info/Journals/Article/SONG/10968296.pdf google scholar
  • Yim, S. K., Kim, K., Chun, S., Oh, T., Jung, W., Jung, K., & Yun, C. H. (2020). Screening of human CYP1A2 and CYP3A4 inhibitors from seaweed in silico and in vitro. Marine Drugs, 18(12), 603-618. https://doi.org/10.3390/md18120603 google scholar

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APA

Lazarova, I., Mateev, E., & Zengin, G. (2025). In silico studies concerning the cytotoxic potential and the inhibition of cytochrome P450 of some bioactive compounds present in Asphodeline lutea root extracts. İstanbul Journal of Pharmacy, 55(1), 58-66. https://doi.org/10.26650/IstanbulJPharm.2025.1545031


AMA

Lazarova I, Mateev E, Zengin G. In silico studies concerning the cytotoxic potential and the inhibition of cytochrome P450 of some bioactive compounds present in Asphodeline lutea root extracts. İstanbul Journal of Pharmacy. 2025;55(1):58-66. https://doi.org/10.26650/IstanbulJPharm.2025.1545031


ABNT

Lazarova, I.; Mateev, E.; Zengin, G. In silico studies concerning the cytotoxic potential and the inhibition of cytochrome P450 of some bioactive compounds present in Asphodeline lutea root extracts. İstanbul Journal of Pharmacy, [Publisher Location], v. 55, n. 1, p. 58-66, 2025.


Chicago: Author-Date Style

Lazarova, Irina, and Emilio Mateev and Gökhan Zengin. 2025. “In silico studies concerning the cytotoxic potential and the inhibition of cytochrome P450 of some bioactive compounds present in Asphodeline lutea root extracts.” İstanbul Journal of Pharmacy 55, no. 1: 58-66. https://doi.org/10.26650/IstanbulJPharm.2025.1545031


Chicago: Humanities Style

Lazarova, Irina, and Emilio Mateev and Gökhan Zengin. “In silico studies concerning the cytotoxic potential and the inhibition of cytochrome P450 of some bioactive compounds present in Asphodeline lutea root extracts.” İstanbul Journal of Pharmacy 55, no. 1 (Aug. 2025): 58-66. https://doi.org/10.26650/IstanbulJPharm.2025.1545031


Harvard: Australian Style

Lazarova, I & Mateev, E & Zengin, G 2025, 'In silico studies concerning the cytotoxic potential and the inhibition of cytochrome P450 of some bioactive compounds present in Asphodeline lutea root extracts', İstanbul Journal of Pharmacy, vol. 55, no. 1, pp. 58-66, viewed 17 Aug. 2025, https://doi.org/10.26650/IstanbulJPharm.2025.1545031


Harvard: Author-Date Style

Lazarova, I. and Mateev, E. and Zengin, G. (2025) ‘In silico studies concerning the cytotoxic potential and the inhibition of cytochrome P450 of some bioactive compounds present in Asphodeline lutea root extracts’, İstanbul Journal of Pharmacy, 55(1), pp. 58-66. https://doi.org/10.26650/IstanbulJPharm.2025.1545031 (17 Aug. 2025).


MLA

Lazarova, Irina, and Emilio Mateev and Gökhan Zengin. “In silico studies concerning the cytotoxic potential and the inhibition of cytochrome P450 of some bioactive compounds present in Asphodeline lutea root extracts.” İstanbul Journal of Pharmacy, vol. 55, no. 1, 2025, pp. 58-66. [Database Container], https://doi.org/10.26650/IstanbulJPharm.2025.1545031


Vancouver

Lazarova I, Mateev E, Zengin G. In silico studies concerning the cytotoxic potential and the inhibition of cytochrome P450 of some bioactive compounds present in Asphodeline lutea root extracts. İstanbul Journal of Pharmacy [Internet]. 17 Aug. 2025 [cited 17 Aug. 2025];55(1):58-66. Available from: https://doi.org/10.26650/IstanbulJPharm.2025.1545031 doi: 10.26650/IstanbulJPharm.2025.1545031


ISNAD

Lazarova, Irina - Mateev, Emilio - Zengin, Gökhan. “In silico studies concerning the cytotoxic potential and the inhibition of cytochrome P450 of some bioactive compounds present in Asphodeline lutea root extracts”. İstanbul Journal of Pharmacy 55/1 (Aug. 2025): 58-66. https://doi.org/10.26650/IstanbulJPharm.2025.1545031



ZAMAN ÇİZELGESİ


Gönderim08.09.2024
Kabul04.02.2025
Çevrimiçi Yayınlanma07.05.2025

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