Startseite In vitro antibacterial activities, DPPH radical scavenging, and molecular simulation of isolated compounds from the leaves of Rhus ruspolii
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

In vitro antibacterial activities, DPPH radical scavenging, and molecular simulation of isolated compounds from the leaves of Rhus ruspolii

  • Tolessa Duguma , Yadessa Melaku EMAIL logo , Daniel Rentsch , Akalu Terfa und Kebede Shenkute
Veröffentlicht/Copyright: 23. September 2024
Veröffentlichen auch Sie bei De Gruyter Brill

Abstract

Rhus ruspolii Engl. plant is traditionally used in Ethiopia to treat various diseases. However, the biological and phytochemical properties of the leaves are not well documented. Hence, this study aimed to isolate phytochemicals from R. ruspolii leaves and evaluate their antibacterial and DPPH radical scavenging activities. GC-MS analysis identified 16 compounds from combined fractions 6–10. Chromatographic separation and NMR analysis resulted in the isolation and characterization of palmitic acid (7), 3,4-dihydroxybenzoic acid (17), cupressuflavone (18), amentoflavone (19), shikimic acid (20), avicularin (21), and myricetin-3-O-5′′-acetylarabinofuranoside (22). The inhibition zones of extracts (100 mg/mL) and isolated compounds (5 mg/mL) ranged from 8.33 ± 0.50 to 16.33 ± 0.47 mm against all evaluated bacteria. Of all isolated compounds, compounds 18 and 21 showed good activity against Gram-negative (supported by in silico molecular docking studies) and Gram-positive bacteria, respectively. The lowest (49.1 %) and the highest (91.3 %) DPPH radicals were inhibited by combined fractions 6–10 and compound 17, respectively, at 62.5 μg/mL. The SwissADME online analysis showed compounds 17 and 20 have good solubility and permeability. The Pro Tox 3.0 online analysis revealed none of the isolated compounds are fatal if swallowed. Therefore, the findings of this study support the traditional use of the plant for treating bacteria diseases.


Corresponding author: Yadessa Melaku, Department of Applied Chemistry, Adama Science and Technology University, P.O. Box: 1888, Adama, Ethiopia, E-mail:

Acknowledgments

The authors acknowledge Adama Science and Technology University for financial and material support and Mr. Muktar Ahmed for conducting antibacterial activity.

  1. Research ethics: Not applicable.

  2. Author contributions: TD planned the study, carried out the investigation, analyzed, interpreted the data, wrote, and edited the original draft of the manuscript. YM planned the study, supervised, analyzed, interpreted the data, reviewed, and edited the manuscript. DR recorded, interpreted NMR spectral data, and reviewed the manuscript. AT planned and supervised the study. KS conducted GC-MS analysis.

  3. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  4. Conflict of interest: The authors state no conflict of interest.

  5. Research funding: Not declared.

  6. Data availability: All data generated or analyzed during this study are included in this published article and provided in supplementary material files.

References

1. JSTOR. Global plants [Internet]. [cited 2024 July 12]. Available from: https://plants.jstor.org/.Suche in Google Scholar

2. POWO. Plants of the world online. Facilitated by the Royal Botanic Gardens, Kew. [Internet]. https://powo.science.kew.org/ [accessed 19 May 2022].Suche in Google Scholar

3. Megersa, M, Asfaw, Z, Kelbessa, E, Beyene, A, Woldeab, B. An ethnobotanical study of medicinal plants in Wayu Tuka district, East Welega zone of Oromia regional state, west Ethiopia. J Ethnobiol Ethnomed 2013;9:68. https://doi.org/10.1186/1746-4269-9-68.Suche in Google Scholar PubMed PubMed Central

4. Giday, M, Asfaw, Z, Woldu, Z. Medicinal plants of the Meinit ethnic group of Ethiopia: an ethnobotanical study. J Ethnopharmacol 2009;124:513–21. https://doi.org/10.1016/j.jep.2009.05.009.Suche in Google Scholar PubMed

5. Birhanu, T, Abera, D, Ejeta, E. Ethnobotanical study of medicinal plants in selected Horro Gudurru Woredas, western Ethiopia. J Biol Agric Healthc 2015;5:83–93.Suche in Google Scholar

6. Bogale, M, Sasikumar, JM, Egigu, MC. An ethnomedicinal study in Tulo district, West Hararghe zone, Oromia region, Ethiopia. Heliyon 2023;9:e15361. https://doi.org/10.1016/j.heliyon.2023.e15361.Suche in Google Scholar PubMed PubMed Central

7. Njoroge, P, Opiyo, S. Antimicrobial activity of root bark extracts of Rhus natalensisa and Rhus ruspolii. Basic Sci Med 2019;8:23–8.Suche in Google Scholar

8. Deresa, DA, Abdissa, Z, Gurmessa, GT, Bedane, KG, Frese, M, Sewald, N, et al.. Biflavonoids from the roots of Rhus ruspolii and evaluations of their antioxidant activities. Bull Chem Soc Ethiop 2022;36:667–74.10.4314/bcse.v36i3.15Suche in Google Scholar

9. Dinku, W, Un, CS, Lee, SH, Jung, YS, Sung, NZ, Dekebo, A. Antiproliferative effect of sterols from resin of Commiphora habessinica. J Pharm Nutr Sci 2019;9:71–80.10.29169/1927-5951.2019.09.02.3Suche in Google Scholar

10. Kim, S, Chen, J, Cheng, T, Gindulyte, A, He, J, He, S, et al.. PubChem 2023 update. Nucleic Acids Res 2023;51:D1373–80. https://doi.org/10.1093/nar/gkac956.Suche in Google Scholar PubMed PubMed Central

11. Hudzicki, J. Kirby-Bauer disk diffusion susceptibility test protocol. [Internet]. https://asm.org/getattachment/2594ce26-bd44-47f6-8287-0657aa9185ad/Kirby-Bauer-Disk-Diffusion-Susceptibility-Test-Protocol-pdf.pdf [accessed 7 Mar 2024].Suche in Google Scholar

12. Grujic, S, Radojevic, I, Vasic, S, Comic, L, Topuzovic, M. Antimicrobial activity and some phytochemical analysis of two extracts Vinca minor L. Kragujevac J Sci 2014;36(2014):145–54. https://doi.org/10.5937/kgjsci1436145g.Suche in Google Scholar

13. Khlifi, D, Hamdi, M, Hayouni, AE, Cazaux, S, Souchard, JP, Couderc, F, et al.. Global chemical composition and antioxidant and anti-tuberculosis activities of various extracts of Globularia alypum L. (Globulariaceae) Leaves. Molecules 2011;16:10592–603. https://doi.org/10.3390/molecules161210592.Suche in Google Scholar PubMed PubMed Central

14. Costenaro, L, Grossmann, JG, Ebel, C, Maxwell, A. Modular structure of the full-Length DNA gyrase B subunit revealed by small-angle X-ray scattering. Structure 2007;15:329–39. https://doi.org/10.1016/j.str.2007.01.013.Suche in Google Scholar PubMed

15. Coleman, JP, Hudson, LL, McKnight, SL, Farrow, JM, Calfee, MW, Lindsey, CA, et al.. Pseudomonas aeruginosa PqsA is an anthranilate-coenzyme A ligase. J Bacteriol 2008;190:1247–55. https://doi.org/10.1128/jb.01140-07.Suche in Google Scholar

16. Mazurek, S. Pyruvate kinase type M2: a key regulator of the metabolic budget system in tumor cells. Int J Biochem Cell Biol 2011;43:969–80. https://doi.org/10.1016/j.biocel.2010.02.005.Suche in Google Scholar PubMed

17. Zahra, K, Dey, T, Ashish, Mishra, SP, Pandey, U. Pyruvate kinase M2 and cancer: the role of PKM2 in promoting tumorigenesis. Front Oncol 2020;10. https://doi.org/10.3389/fonc.2020.00159.Suche in Google Scholar PubMed PubMed Central

18. Wu, CC, Li, TK, Farh, L, Lin, LY, Lin, TS, Yu, YJ, et al.. Structural basis of type II topoisomerase inhibition by the anticancer drug etoposide. Science 2011;333:459–62. https://doi.org/10.1126/science.1204117.Suche in Google Scholar PubMed

19. Rizvi, SMD, Shakil, S, Haneef, M. A simple click by click protocol to perform docking: AutoDock 4.2 made easy for non-bioinformaticians. EXCLI J 2013;12:831–57.Suche in Google Scholar

20. BIOVA. Dassault systemes, discovery studio visualizer. [Internet]. https://discover.3ds.com/discovery-studio-visualizer-download [accessed 7 Mar 2024].Suche in Google Scholar

21. Berman, HM. The protein data bank. Nucleic Acids Res 2000;28:235–42. https://doi.org/10.1093/nar/28.1.235.Suche in Google Scholar PubMed PubMed Central

22. Daina, A, Michielin, O, Zoete, V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 2017;7:1–12. https://doi.org/10.1038/srep42717.Suche in Google Scholar PubMed PubMed Central

23. Banerjee, P, Kemmler, E, Dunkel, M, Preissner, R. ProTox 3.0: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Res 2024:1–8. https://doi.org/10.1093/nar/gkae303.Suche in Google Scholar PubMed PubMed Central

24. Premjanu, N, Jaynthy, C. Antimicrobial activity of diethyl phthalate: an insilico approach. Asian J Pharmaceut Clin Res 2014;7:141–2.Suche in Google Scholar

25. Yasmin, F, Nazli, Zi H, Shafiq, N, Aslam, M, Bin Jardan, YA, Nafidi, HA, et al.. Plant- based bioactive phthalates derived from Hibiscus rosa-sinensis: as in vitro and in silico enzyme inhibition. ACS Omega 2023;8:32677–89. https://doi.org/10.1021/acsomega.3c03342.Suche in Google Scholar PubMed PubMed Central

26. Liu, J, Fernandez, D, Gao, Y, Silvie, P, Gao, Y, Dai, G. Enzymology, histological and ultrastructural effects of Ar-turmerone on Culex pipiens pallens Larvae. Insects 2020;11:336. https://doi.org/10.3390/insects11060336.Suche in Google Scholar PubMed PubMed Central

27. Selmy, A, Hegazy, M, El-Hela, A, Saleh, A, El-Hamouly, M. In vitro and in silico studies of neophytadiene; a diterpene isolated from Aeschynomene elaphroxylon (Guill. & Perr.) Taub. as apoptotic. Egypt. J Chem 2023;66:149–61.10.21608/ejchem.2023.178261.7296Suche in Google Scholar

28. Morteza-Semnani, K, Saeedi, M, Akbarzadeh, M. Chemical composition and antimicrobial activity of the essential oil of Verbascum thapsus L. J Essent Oil-Bear Plants 2012;15:373–9. https://doi.org/10.1080/0972060x.2012.10644063.Suche in Google Scholar

29. Ananthi, P, Ranjitha Kumari, BD. GC - MS determination of bioactive components of Rorippa indica L. Int J ChemTech Res 2013;5:2027–33.Suche in Google Scholar

30. Salem, MZM, Zayed, MZ, Ali, HM, El-Kareem, MSMA. Chemical composition, antioxidant and antibacterial activities of extracts from Schinus molle wood branch growing in Egypt. J Wood Sci 2016;62:548–61. https://doi.org/10.1007/s10086-016-1583-2.Suche in Google Scholar

31. Vanitha, V, Vijayakumar, S, Nilavukkarasi, M, Punitha, VN, Vidhya, E, Praseetha, PK. Heneicosane—a novel microbicidal bioactive alkane identified from Plumbago zeylanica L. Ind Crops Prod 2020;154:112748. https://doi.org/10.1016/j.indcrop.2020.112748.Suche in Google Scholar

32. Faridha Begum, I, Mohankumar, R, Jeevan, M, Ramani, K. GC–MS Analysis of bio- active molecules derived from Paracoccus pantotrophus FMR19 and the antimicrobial activity against bacterial pathogens and MDROs. Indian J Microbiol 2016;56:426–32. https://doi.org/10.1007/s12088-016-0609-1.Suche in Google Scholar PubMed PubMed Central

33. Umar, H, Aliyu, MR, Usman, AG, Ghali, UM, Abba, SI, Ozsahin, DU. Prediction of cell migration potential on human breast cancer cells treated with Albizia lebbeck ethanolic extract using extreme machine learning. Sci Rep 2023;13:22242. https://doi.org/10.1038/s41598-023-49363-z.Suche in Google Scholar PubMed PubMed Central

34. Ekeocha, PA, Ezeh, CO, Anyam, JV, Onyekwelu, KC, Ikekpeazu, J, Igoli, JO. Isolation, structural elucidation and therapeutic potentials of root of Cucurbita pepo. Indian J Pharmaceut Sci 2021;83:1288–94. https://doi.org/10.36468/pharmaceutical-sciences.884.Suche in Google Scholar

35. National Institute of Advanced Industrial Science and Technology (AIST). Spectral database for organic compounds SDBS. SDBS-13C NMR of hexadecanoic acid. SDBS No. 908CDS-00-855; 1999.Suche in Google Scholar

36. Nguyen, DMC, Seo, DJ, Kim, KY, Park, RD, Kim, DH, Han, YS, et al.. Nematicidal activity of 3,4-dihydroxybenzoic acid purified from Terminalia nigrovenulosa bark against Meloidogyne incognita. Microb Pathog 2013;59–60:52–9. https://doi.org/10.1016/j.micpath.2013.04.005.Suche in Google Scholar PubMed

37. Wang, H, Wang, H, Wang, J, Wang, Q, Ma, Qfeng, Chen, Y. Protocatechuic acid inhibits inflammatory responses in LPS-stimulated BV2 Microglia via NF-κB and MAPKs signaling pathways. Neurochem Res 2015;40:1655–60. https://doi.org/10.1007/s11064-015-1646-6.Suche in Google Scholar PubMed

38. Gallardo-Fernández, M, Hornedo-Ortega, R, Cerezo, AB, Troncoso, AM, García-Parrilla, MC. Melatonin, protocatechuic acid and hydroxytyrosol effects on vitagenes system against alpha-synuclein toxicity.Food Chem Toxicol. 2019;134:110817. https://doi.org/10.1016/j.fct.2019.110817.Suche in Google Scholar PubMed

39. Adedara, IA, Okpara, ES, Busari, EO, Omole, O, Owumi, SE, Farombi, EO. Dietary protocatechuic acid abrogates male reproductive dysfunction in streptozotocin-induced diabetic rats via suppression of oxidative damage, inflammation and caspase-3 activity. Eur J Pharmacol 2019;849:30–42. https://doi.org/10.1016/j.ejphar.2019.01.033.Suche in Google Scholar PubMed

40. Safaeian, L, Emami, R, Hajhashemi, V, Haghighatian, Z. Antihypertensive and antioxidant effects of protocatechuic acid in deoxycorticosterone acetate-salt hypertensive rats. Biomed Pharmacother 2018;100:147–55. https://doi.org/10.1016/j.biopha.2018.01.107.Suche in Google Scholar PubMed

41. Chari, VM, Ilyas, M, Wagner, H, Neszmélyi, A, Fa-Ching, C, Li-Kuang, C, et al.. 13C-NMR spectroscopy of biflavanoids. Phytochemistry 1977;16:1273–8. https://doi.org/10.1016/s0031-9422(00)94373-5.Suche in Google Scholar

42. Al-Sayed, E, Abdel-Daim, M. Protective role of cupressuflavone from Cupressus macrocarpa against carbon tetrachloride-induced hepato- and nephrotoxicity in mice. Planta Med 2014;80:1665–71. https://doi.org/10.1055/s-0034-1383211.Suche in Google Scholar PubMed

43. Al‐Sayed, E, Gad, HA, El‐Shazly, M, Abdel‐Daim, MM, Nasser Singab, A. Anti‐inflammatory and analgesic activities of cupressuflavone from Cupressus macrocarpa: impact on pro‐inflammatory mediators. Drug Dev Res 2018;79:22–8. https://doi.org/10.1002/ddr.21417.Suche in Google Scholar PubMed

44. Sani, A, Alemika, T, Sule, I, Ilyas, M, Haruna, A, Sikira, A. Isolation and characterisation of cupressuflavone from the leaves of Lophira lanceolata. J Pharm Bioresour 2011;7. https://doi.org/10.4314/jpb.v7i1.67748.Suche in Google Scholar

45. Ambarwati, NSS, Elya, B, Malk, A, Hanafi, M, Awang, MSN. Isolation, identification, and antibacterial of amentoflavone from Garcinia latissima Miq. Leaves. Int J Appl Pharm 2022:67–73. https://doi.org/10.22159/ijap.2022.v14s3.13.Suche in Google Scholar

46. Markham, K R, Sheppard, C, Geiger, H. 13C NMR studies of some naturally occurring amentoflavone and hinokiflavone biflavonoids. Phytochemistry 1987;26:3335–7. https://doi.org/10.1016/s0031-9422(00)82499-1.Suche in Google Scholar

47. Arwa, PS, Zeraik, ML, Ximenes, VF, da Fonseca, LM, Bolzani, V da S, Silva, DHS. Redox-active biflavonoids from Garcinia brasiliensis as inhibitors of neutrophil oxidative burst and human erythrocyte membrane damage. J Ethnopharmacol 2015;174:410–8. https://doi.org/10.1016/j.jep.2015.08.041.Suche in Google Scholar PubMed

48. Pei, JS, Liu, CC, Hsu, YN, Lin, LL, Wang, SC, Chung, JG, et al.. Amentoflavone induces cell-cycle arrest and apoptosis in MCF-7 human breast cancer cells via mitochondria-dependent pathway. In Vivo 2012;26:963–70.Suche in Google Scholar

49. Laishram, S, Sheikh, Y, Moirangthem, DS, Deb, L, Pal, BC, Talukdar, NC, et al.. Anti-diabetic molecules from Cycas pectinata Griff. traditionally used by the Maiba-Maibi. Phytomedicine 2015;22:23–6. https://doi.org/10.1016/j.phymed.2014.10.007.Suche in Google Scholar PubMed

50. Wilsky, S, Sobotta, K, Wiesener, N, Pilas, J, Althof, N, Munder, T, et al.. Inhibition of fatty acid synthase by amentoflavone reduces coxsackievirus B3 replication. Arch Virol 2012;157:259–69. https://doi.org/10.1007/s00705-011-1164-z.Suche in Google Scholar PubMed

51. Venditti, A, Frezza, C, Sciubba, F, Foddai, S, Serafini, M, Bianco, A. Terpenoids and more polar compounds from the male cones of Wollemia nobilis. Chem Biodivers 2017;14. https://doi.org/10.1002/cbdv.201600332.Suche in Google Scholar PubMed

52. Rabelo, TK, Zeidán-Chuliá, F, Caregnato, FF, Schnorr, CE, Gasparotto, J, Serafini, MR, et al.. In vitro neuroprotective effect of shikimic acid against hydrogen peroxide-induced oxidative stress. J Mol Neurosci 2015;56:956–65. https://doi.org/10.1007/s12031-015-0559-9.Suche in Google Scholar PubMed

53. Veach, D, Hosking, H, Thompson, K, Santhakumar, AB. Anti-platelet and anti-thrombogenic effects of shikimic acid in sedentary population. Food Funct 2016;7:3609–16. https://doi.org/10.1039/c6fo00927a.Suche in Google Scholar PubMed

54. Li, X, Mo, K, Tian, G, Zhou, J, Gong, J, Li, L, et al.. Shikimic acid regulates the NF- κB/MAPK signaling pathway and gut microbiota to ameliorate DSS-induced ulcerative colitis. J Agric Food Chem 2023;71:8906–14. https://doi.org/10.1021/acs.jafc.3c00283.Suche in Google Scholar PubMed PubMed Central

55. Zhang, H, Li, G, Han, R, Zhang, R, Ma, X, Wang, M, et al.. Antioxidant, anti-inflammatory, and cytotoxic properties and chemical compositions of Filipendula palmata (Pall.) Maxim. Evid base Compl Altern Med 2021;2021:1–12. https://doi.org/10.1155/2021/6659620.Suche in Google Scholar PubMed PubMed Central

56. Ugheighele, SE, Imafidon, KE, Choudhary, MI, Shakil, A, Okoro, EE. Isolation of Quercetin and avicularin from Dennettia tripetala (G. Baker) Seeds, and evaluation of the oxidative stress Management capacity and cytotoxic activities of its acetone extract and fractions. Chem Afr 2022;5:1275–85. https://doi.org/10.1007/s42250-022-00413-5.Suche in Google Scholar

57. Nor, I, Wirasutisna, KR, Hartati, R, Insanu, M. The α-glucosidase inhibitory activity of avicularin and 4-O-methyl gallic acid isolated from Syzygium myrtifolium leaves. Saudi Pharmaceut J 2023;31. https://doi.org/10.1016/j.jsps.2023.06.010.Suche in Google Scholar PubMed PubMed Central

58. Wang, Z, Li, F, Quan, Y, Shen, J. Avicularin ameliorates human hepatocellular carcinoma via the regulation of NF-κB/COX-2/PPAR-γ activities. Mol Med Rep 2019:5417–23. https://doi.org/10.3892/mmr.2019.10198.Suche in Google Scholar PubMed PubMed Central

59. Zou, Zling, Hui, SM, feng, YW, Yang, L, yi, KL. Avicularin suppresses cartilage extracellular matrix degradation and inflammation via TRAF6/MAPK activation. Phytomedicine 2021;91:153657. https://doi.org/10.1016/j.phymed.2021.153657.Suche in Google Scholar PubMed

60. Samant, NP, Gupta, GL. Avicularin attenuates memory impairment in rats with amyloid beta-induced Alzheimer’s disease. Neurotox Res 2022;40:140–53. https://doi.org/10.1007/s12640-021-00467-2.Suche in Google Scholar PubMed

61. Torres-Mendoza, D, González, J, Ortega-Barría, E, Heller, MV, Capson, TL, McPhail, K, et al.. Weakly antimalarial flavonol arabinofuranosides from Calycolpus arszewiczianus. J Nat Prod 2006;69:826–8. https://doi.org/10.1021/np050484i.Suche in Google Scholar PubMed

62. Alam, P, Parvez, MK, Arbab, AH, Siddiqui, NA, Al-Dosary, MS, Al-Rehaily, AJ, et al.. Inter-species comparative antioxidant assay and HPTLC analysis of sakuranetin in the chloroform and ethanol extracts of aerial parts of Rhus retinorrhoea and Rhus tripartita. Pharm Biol 2017;55:1450–7. https://doi.org/10.1080/13880209.2017.1304428.Suche in Google Scholar PubMed PubMed Central

63. Rekik, I, Ben Ameur, R, Ayadi, W, Soussi, A, Gargouri, A, Allouche, N. Anti-oxidant, anti-diabetic and anti-lipidemic activities of root bark extracts from Rhus tripartitum and cytotoxicity evaluation of isolated compounds. South Afr J Bot 2022;147:71–80. https://doi.org/10.1016/j.sajb.2021.12.038.Suche in Google Scholar

64. Blois, MS. Antioxidant determinations by the use of a stable free radical. Nature 1958;181:1199–200. https://doi.org/10.1038/1811199a0.Suche in Google Scholar

65. Ali, HM, Abo-Shady, A, Sharaf Eldeen, HA, Soror, HA, Shousha, WG, Abdel-Barry, OA, et al.. Structural features, kinetics and SAR study of radical scavenging and antioxidant activities of phenolic and anilinic compounds. Chem Cent J 2013;7:53. https://doi.org/10.1186/1752-153x-7-53.Suche in Google Scholar

66. Nofrizal, PDP, Arbain, D. Antioxidant and antibacterial constituents from two Sumatran Ferns, Trichomanes javanicum and Oleandra pistillaris. Nat Prod Commun 2017;12:1263–4.10.1177/1934578X1701200829Suche in Google Scholar

67. LeBel, M. Ciprofloxacin: chemistry, mechanism of action, resistance, antimicrobial spectrum, pharmacokinetics, clinical trials, and adverse reactions. Pharmacotherapy 1988;8:3–30. https://doi.org/10.1002/j.1875-9114.1988.tb04058.x.Suche in Google Scholar PubMed

68. Ivanova, L, Karelson, M. The impact of software used and the type of target protein on molecular docking accuracy. Molecules 2022;27. https://doi.org/10.3390/molecules27249041.Suche in Google Scholar PubMed PubMed Central

69. Calfee, MW, Coleman, JP, Pesci, EC. Interference with Pseudomonas quinolone signal synthesis inhibits virulence factor expression by Pseudomonas aeruginosa. Proc Natl Acad Sci. 2001;98(20):11633–7, https://doi.org/10.1073/pnas.201328498.Suche in Google Scholar PubMed PubMed Central

70. Pfeiffer, T, Schuster, S, Bonhoeffer, S. Cooperation and competition in the evolution of ATP-producing pathways. Science 2001;292:504–7. https://doi.org/10.1126/science.1058079.Suche in Google Scholar PubMed

71. Park, JH, Kundu, A, Lee, SH, Jiang, C, Lee, SH, Kim, YS, et al.. Specific pyruvate kinase M2 inhibitor, compound 3K, induces autophagic cell death through disruption of the glycolysis pathway in ovarian cancer cells. Int J Biol Sci 2021;17:1895–908. https://doi.org/10.7150/ijbs.59855.Suche in Google Scholar PubMed PubMed Central

72. Linka, RM, Porter, ACG, Volkov, A, Mielke, C, Boege, F, Christensen, MO. C-Terminal regions of topoisomerase II and II determine isoform-specific functioning of the enzymes in vivo. Nucleic Acids Res 2007;35:3810–22. https://doi.org/10.1093/nar/gkm102.Suche in Google Scholar PubMed PubMed Central

73. Turley, H, Comley, M, Houlbrook, S, Nozaki, N, Kikuchi, A, Hickson, I, et al.. The distribution and expression of the two isoforms of DNA topoisomerase II in normal and neoplastic human tissues. Br J Cancer 1997;75:1340–6. https://doi.org/10.1038/bjc.1997.227.Suche in Google Scholar PubMed PubMed Central

74. Lipinski, CA, Lombardo, F, Dominy, BW, Feeney, PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 2012;64:4–17. https://doi.org/10.1016/j.addr.2012.09.019.Suche in Google Scholar


Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/znc-2024-0127).


Received: 2024-05-29
Accepted: 2024-09-05
Published Online: 2024-09-23
Published in Print: 2025-05-26

© 2024 Walter de Gruyter GmbH, Berlin/Boston

Heruntergeladen am 6.11.2025 von https://www.degruyterbrill.com/document/doi/10.1515/znc-2024-0127/html?lang=de
Button zum nach oben scrollen