SavedAdd your journal

Journals / Ankara Üniversitesi Eczacılık Fakültesi Dergisi / 2026 / Cilt: 44 Sayı: 2

TOPOISOMERASE II ENZYME INHIBITORS

TOPOİZOMERAZ II ENZİM İNHİBİTÖRLERİ

Oğuzhan Fırat(HACETTEPE ÜNİVERSİTESİ, ECZACILIK FAKÜLTESİ)0000-0002-8726-8530
İlkay Yıldız(ANKARA ÜNİVERSİTESİ, ECZACILIK FAKÜLTESİ)0000-0001-9526-0232
Pages
356–372
Publication Date
2020-05-31
🏛️Bibliographic metadata and full text access for this article are provided via DergiPark.
DergiPark Record ↗
✨

AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

In this context, compounds with clinical uses as well as certain compounds which are in the developmental stage are included.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Objective: The use of topoisomerase II enzyme inhibitors, which have increased in importance in recent years, has been evaluated in terms of pharmaceutical chemistry and clinical use.
📊
Key Findings & Data:Objective: The use of topoisomerase II enzyme inhibitors, which have increased in importance in recent years, has been evaluated in terms of pharmaceutical chemistry and clinical use.
💡
Conclusion & Impact:In this context, compounds with clinical uses as well as certain compounds which are in the developmental stage are included.
🔬Design:Derleme
📍Scope:Comprehensive Sample
⚙️Variables:antikanser · klinik eczacılık · topoizomeraz II

Abstract

Objective: The use of topoisomerase II enzyme inhibitors, which have increased in importance in recent years, has been evaluated in terms of pharmaceutical chemistry and clinical use. In this context, compounds with clinical uses as well as certain compounds which are in the developmental stage are included.

Özet

Amaç: Son yıllarda önemi daha da artan topoizomeraz II enzim inhibitörleri’nin Farmasötik Kimya bilimi açısından ve klinik kullanımları değerlendirilmiştir. Bu bağlamda, klinik kullanımları olan bileşiklerin yanında geliştirilme aşamasında olan bazı bileşiklere de yer verilmiştir.

🔖

Cite This Article

Fırat, O., Yıldız, İ. (2020). TOPOISOMERASE II ENZYME INHIBITORS. Ankara Üniversitesi Eczacılık Fakültesi Dergisi, Cilt: 44 Sayı: 2, 356–372. https://doi.org/10.33483/jfpau.696349

📄 Full Text PDF Viewer

📄

PDF görüntüleyici hazırlanıyor...

References (56)

  1. Harrington, K. J. (2011). Biology of cancer. Medicine, 39(12), 689-692. https://doi.org/10.1016/j.mpmed.2011.09.015
  2. Wong, S. H., Kwong, T. N., Wu, C. Y., Yu, J. (2019). Clinical applications of gut microbiota in cancer biology. Seminars in cancer biology, 55, 28-36. https://doi.org/10.1016/j.semcancer.2018.05.003
  3. Prospective Studies Collaboration. (2002). Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. The Lancet, 360(9349), 1903-1913. https://doi.org/10.1016/S0140-6736(02)11911-8
  4. Bilge, D. B., Kantarcı, G. Mutation, Dna Damage, Repair Mechanisms And The Relation Of Cancer. Ankara Üniversitesi Eczacılık Fakültesi Dergisi, 35(2), 149-170. https://doi.org/10.1501/Eczfak_0000000056
  5. Friedberg, E. C. (2003). DNA damage and repair. Nature, 421(6921), 436-440. https://doi.org/10.1038/nature01408
  6. Doğan, İ., Yar, A. S., Ergin, V., Menevşe, S., Menevşe, A., Ekmekçi, A. (2013). L929 Fibroblast Hücre Hattında Topoizomeraz İnhibisyonunun DNA Onarımı ve Apoptozis Üzerine Etkisi. Turkish Journal of Biochemistry/Türk Biyokimya Dergisi, 38(2), 229-237. doi:10.5505/tjb.2013.32032
  7. Pommier, Y. (2012). DNA topoisomerases and cancer, Springer, Berlin.
  8. Cuya, S. M., Bjornsti, M. A., van Waardenburg, R. C. (2017). DNA topoisomerase-targeting chemotherapeutics: what’s new?. Cancer chemotherapy and pharmacology, 80 (1), 1-14. https://doi.org/10.1007/s00280-017-3334-5
  9. Baker, N. M., Rajan, R., Mondragon, A. (2009). Structural studies of type I topoisomerases. Nucleic acids research, 37(3), 693-701. https://doi.org/10.1093/nar/gkn1009
  10. Pendleton, M., Lindsey Jr, R. H., Felix, C. A., Grimwade, D., Osheroff, N. (2014). Topoisomerase II and leukemia. Annals of the New York Academy of Sciences, 1310(1), 98-110. https://doi.org/10.1111/nyas.12358
  11. Bansal, S., Bajaj, P., Pandey, S., Tandon, V. (2017). Topoisomerases: Resistance versus sensitivity, how far we can go?. Medicinal research reviews, 37(2), 404-438. https://doi.org/10.1002/med.21417
  12. Holden, J. A. (2001). DNA Topoisomerases as anticancer drug targets from the laboratory to the clinic. Current Medicinal Chemistry-Anti-Cancer Agents, 1(1), 1-25. https://doi.org/10.2174/1568011013354859
  13. Hande, K. R. (2008). Topoisomerase II inhibitors. Update on cancer therapeutics, 3(1), 13-26. https://doi.org/10.1016/j.uct.2008.02.001
  14. DeVita, V. T., Lawrence, T. S., Rosenberg, S. A. (2019). Cancer: principles & practice of oncology: primer of the molecular biology of cancer (Vol. 11): Lippincott Williams & Wilkins. Philadelphia.
  15. Speth, P. A. J., Van Hoesel, Q. G. C. M., Haanen, C. (1988). Clinical pharmacokinetics of doxorubicin. Clinical pharmacokinetics, 15(1), 15-31. https://doi.org/10.2165/00003088-198815010-00002
  16. Rizvi, S. F. A., Tariq, S., Mehdi, M. (2018). Anthracyclines: mechanism of action, classification, pharmacokinetics and future–a mini review. Int J Biotech Bioeng, 4(4), 81-85.
  17. Albert, J., Verweij, J., Loos, W. J., Sparreboom, A. (2003). Pharmacological effects of formulation vehicles. Clinical pharmacokinetics, 42(7), 665-685. https://doi.org/10.2165/00003088-200342070-00005
  18. Clark, P. I., Slevin, M. L. (1987). The clinical pharmacology of etoposide and teniposide. Clinical pharmacokinetics, 12(4), 223-252. https://doi.org/10.2165/00003088-198712040-00001
  19. Donelli, M. G., Zucchetti, M., Munzone, E., D’Incalci, M., Crosignani, A. (1998). Pharmacokinetics of anticancer agents in patients with impaired liver function. European journal of cancer, 34(1), 33-46. https://doi.org/10.1016/S0959-8049(97)00340-7
  20. Veal, G. J., Cole, M., Errington, J., Parry, A., Hale, J., Pearson, A. D., Howe K., Chisholm J, C., Beane C., Brennan B., Waters F., Glaser A., Hemsworth S., McDowell H., Wright Y., Pritchard-Jones K., Pinkerton R., Jenner G., Nicholson J., Elsworth A. M., Boddy A. V. (2005). Pharmacokinetics of dactinomycin in a pediatric patient population: a United Kingdom Children's Cancer Study Group Study. Clinical cancer research, 11(16), 5893-5899. https://doi.org /10.1158/1078-0432.CCR-04-2546
  21. Van Hasselt, J. G. C., Van Calsteren, K., Heyns, L., Han, S., Mhallem Gziri, M., Schellens, J. H. M., Beijnen J. H., Huitema A. D. R., Amant, F. (2014). Optimizing anticancer drug treatment in pregnant cancer patients: pharmacokinetic analysis of gestation-induced changes for doxorubicin, epirubicin, docetaxel and paclitaxel. Annals of oncology, 25(10), 2059-2065. https://doi.org/10.1093/annonc/mdu140
  22. Crom, W. R., Glynn-Barnhart, A. M., Rodman, J. H., Teresi, M. E., Kavanagh, R. E., Christensen, M. L., Evans, W. E. (1987). Pharmacokinetics of anticancer drugs in children. Clinical pharmacokinetics, 12(3), 168-213. https://doi.org/10.2165/00003088-198712030-00002
  23. Reid, J. M., Pendergrass, T. W., Krailo, M. D., Hammond, G. D., Ames, M. M. (1990). Plasma pharmacokinetics and cerebrospinal fluid concentrations of idarubicin and idarubicinol in pediatric leukemia patients: a Childrens Cancer Study Group report. Cancer research, 50(20), 6525-6528.
  24. Robert, J. (1993). Clinical pharmacokinetics of idarubicin. Clinical pharmacokinetics, 24(4), 275-288. https://doi.org/10.2165/00003088-199324040-00002
  25. Hall, S. W., Friedman, J., Legha, S. S., Benjamin, R. S., Gutterman, J. U., Loo, T. L. (1983). Human pharmacokinetics of a new acridine derivative, 4′-(9-acridinylamino) methanesulfon-m-anisidide (NSC 249992). Cancer research, 43(7), 3422-3426.
  26. Rather, M. (2016). A comprehensive review on the phytochemical and pharmacological aspects of Podophyllum hexandrum: a high value medicinal plant. Advances in Biomedicine and Pharmacy, 3(4), 216-226. doi:10.19046/abp.v03i04.06
  27. Denny, W. A. (2002). Acridine derivatives as chemotherapeutic agents. Current Medicinal Chemistry, 9(18), 1655-1665. https://doi.org/10.2174/0929867023369277
  28. Dittrich, C., Coudert, B., Paz-Ares, L., Caponigro, F., Salzberg, M., Gamucci, T., Paoletti X., Hermans C., Lacombe D., Fumoleau P., European Organization for Research and Treatment of Cancer--Early Clinical Studies Group/New Drug Development Programme (EORTC-ECSG/NDDP) (2003). Phase II study of XR 5000 (DACA), an inhibitor of topoisomerase I and II, administered as a 120-h infusion in patients with non-small cell lung cancer. European Journal of Cancer, 39(3), 330-334. https://doi.org/10.1016/S0959-8049(02)00559-2
  29. De Souza, P. L., North, S., Bolger, G. B., Spiridonidis, H., Lim, R., Khoo, K. S., Fujimori, M. (2010). A phase II trial of weekly iv KW‐2170 in advanced castrate‐resistant prostate cancer. Asia‐Pacific Journal of Clinical Oncology, 6(4), 292-297. https://doi.org/10.1111/j.1743-7563.2010.01328.x
  30. Wang, J. C. (2009). A journey in the world of DNA rings and beyond. Annual review of biochemistry, 78, 31-54. https://doi.org/10.1146/annurev.biochem.78.030107.090101
  31. Austin, C. A., Marsh, K. L. (1998). Eukaryotic DNA topoisomerase II beta. BioEssays: news and reviews in molecular, cellular and developmental biology, 20(3), 215–226. https://doi.org/10.1002/(SICI)1521-1878(199803)20:3 3.0.CO;2-Q
  32. Marinello, J., Delcuratolo, M., Capranico, G. (2018). Anthracyclines as topoisomerase II poisons: from early studies to new perspectives. International journal of molecular sciences, 19(11), 3480. https://doi.org/10.3390/ijms19113480
  33. Vejpongsa, P., Yeh, E. T. H. (2014). Topoisomerase 2β: a promising molecular target for primary prevention of anthracycline‐induced cardiotoxicity. Clinical Pharmacology & Therapeutics, 95(1), 45-52. https://doi.org/10.1038/clpt.2013.201
  34. Bailly, C. (2012). Contemporary challenges in the design of topoisomerase II inhibitors for cancer chemotherapy. Chemical reviews, 112(7), 3611-3640. https://doi.org/ 10.1021/cr200325f
  35. Nitiss, J. L. (2009). Targeting DNA topoisomerase II in cancer chemotherapy. Nature Reviews Cancer, 9(5), 338-350. https://doi.org/10.1038/nrc2607
  36. Cornarotti, M., Tinelli, S., Willmore, E., Zunino, F., Fisher, L. M., Austin, C. A., Capranico, G. (1996). Drug sensitivity and sequence specificity of human recombinant DNA topoisomerases IIalpha (p170) and IIbeta (p180). Molecular Pharmacology, 50(6), 1463-1471.
  37. Errington, F., Willmore, E., Tilby, M. J., Li, L., Li, G., Li, W., Baguley B. C., Austin, C. A. (1999). Murine transgenic cells lacking DNA topoisomerase IIβ are resistant to acridines and mitoxantrone: analysis of cytotoxicity and cleavable complex formation. Molecular pharmacology, 56(6), 1309-1316. https://doi.org/10.1124/mol.56.6.1309
  38. Hoffmann, D., Berscheid, H. G., Boettger, D., Hermentin, P., Sedlacek, H. H., Kraemer, H. P. (1990). Structure-activity relationship of anthracyclines in vitro. Journal of medicinal chemistry, 33(1), 166-171. https://doi.org/ 10.1021/jm00163a028
  39. Bkhaitan, M. M., Mirza, A. Z., Shamshad, H., Ali, H. I. (2017). Identification of potent virtual leads and ADME prediction of isoxazolidine podophyllotoxin derivatives as topoisomerase II and tubulin inhibitors. Journal of Molecular Graphics and Modelling, 73, 74-93. https://doi.org/10.1016/j.jmgm.2017.01.015
  40. Zhu, L., Cao, X., Chen, W., Zhang, G., Sun, D., Wang, P. G. (2005). Syntheses and biological activities of daunorubicin analogs with uncommon sugars. Bioorganic & medicinal chemistry, 13(23), 6381-6387. https://doi.org/10.1016/j.bmc.2005.06.053
  41. Zheng, S., Zhou, S., Qiao, G., Yang, Q., Zhang, Z., Lin, F., Min D., Tang L., Li H., Sun Y., Zhao H., Shen Z., Yao Y. (2015). Pirarubicin-based chemotherapy displayed better clinical outcomes and lower toxicity than did doxorubicin-based chemotherapy in the treatment of non-metastatic extremity osteosarcoma. American journal of cancer research, 5(1), 411-422.
  42. Murphy, M. B., Mercer, S. L., Deweese, J. E. (2017). Chapter Five Inhibitors and Poisons of Mammalian Type II Topoisomerases. In: Fishbein J.C., Heilman J. M. (Eds.), Advances in Molecular Toxicology (Vol. 11, pp. 203-240), Elsevier.
  43. Miller, C. M., O’Sullivan, E. C., McCarthy, F. O. (2019). Novel 11-substituted ellipticines as potent anticancer agents with divergent activity against cancer cells. Pharmaceuticals, 12(2), 90. https://doi.org/10.3390/ph12020090
  44. Vann, K. R., Ergün, Y., Zencir, S., Oncuoglu, S., Osheroff, N., Topcu, Z. (2016). Inhibition of human DNA topoisomerase IIα by two novel ellipticine derivatives. Bioorganic & medicinal chemistry letters, 26(7), 1809-1812. https://doi.org/10.1016/j.bmcl.2016.02.034
  45. Jamieson, G. C., Fox, J. A., Poi, M., Strickland, S. A. (2016). Molecular and pharmacologic properties of the anticancer quinolone derivative vosaroxin: A new therapeutic agent for acute myeloid leukemia. Drugs, 76(13), 1245-1255. https://doi.org/10.1007/s40265-016-0614-z
  46. Economides, M. P., McCue, D., Borthakur, G., Pemmaraju, N. (2019). Topoisomerase II inhibitors in AML: past, present, and future. Expert opinion on pharmacotherapy, 20(13), 1637-1644. https://doi.org/10.1080/14656566.2019.1621292
  47. Hevener, K., Verstak, T. A., Lutat, K. E., Riggsbee, D. L., Mooney, J. W. (2018). Recent developments in topoisomerase-targeted cancer chemotherapy. Acta pharmaceutica sinica B, 8(6), 844-861. https://doi.org/10.1016/j.apsb.2018.07.008
  48. Barrenetxea Lekue, C., Grasso Cicala, S., Leppä, S., Stauffer Larsen, T., Herráez Rodríguez, S., Alonso Caballero, C., Jørgensen, J. M., Toldbod, H., Leal Martínez, I., D'Amore, F. (2019). Pixantrone beyond monotherapy: a review. Annals of hematology, 98(9), 2025–2033. https://doi.org/10.1007/s00277-019-03749-0
  49. Delgado, J. L., Hsieh, C. M., Chan, N. L., Hiasa, H. (2018). Topoisomerases as anticancer targets. Biochemical Journal, 475(2), 373-398. https://doi.org/10.1042/BCJ20160583
  50. Mir, O., Dahut, W., Goldwasser, F., Heery, C. (2012). Topoisomerase II Inhibitors: Current Use and Prospects. In Y. Pommier (Ed.), DNA Topoisomerases and Cancer (pp. 279-307). New York, NY: Springer New York.
  51. Skok, Z., Zidar, N., Kikelj, D., Ilaš, J. (2019). Dual inhibitors of human DNA topoisomerase II and other cancer-related targets. Journal of medicinal chemistry., https://doi.org/10.1021/acs.jmedchem.9b00726
  52. Larsen, A. K., Escargueil, A. E., Skladanowski, A. (2003). Catalytic topoisomerase II inhibitors in cancer therapy. Pharmacology & therapeutics, 99(2), 167-181. https://doi.org/10.1016/S0163-7258(03)00058-5
  53. Cresteil, T. (2017). Aclarubicin. In Reference Module in Biomedical Sciences: Elsevier.
  54. Swift, L. P., Cutts, S. M., Nudelman, A., Levovich, I., Rephaeli, A., Phillips, D. R. (2008). The cardio-protecting agent and topoisomerase II catalytic inhibitor sobuzoxane enhances doxorubicin-DNA adduct mediated cytotoxicity. Cancer chemotherapy and pharmacology, 61(5), 739-749. https://doi.org/10.1007/s00280-007-0528-2
  55. Ortega, J. A., Riccardi, L., Minniti, E., Borgogno, M., Arencibia, J. M., Greco, M. L., Minarini A. Sissi C., De Vivo, M. (2018). Pharmacophore hybridization to discover novel Topoisomerase II poisons with promising antiproliferative activity. Journal of medicinal chemistry, 61(3), 1375-1379. https://doi.org/10.1021/acs.jmedchem.7b01388
  56. Austin, C. A., Marsh, K. L. (1998). Eukaryotic DNA topoisomerase II beta. BioEssays: news and reviews in molecular, cellular and developmental biology, 20(3), 215–226. https://doi.org/10.1002/(SICI)1521-1878(199803)20:3 3.0.CO;2-Q