TOPOISOMERASE II ENZYME INHIBITORS

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.

Result and Discussion: Topoisomerase II enzyme inhibition targeted cancer chemotherapy and drug development efforts that are suitable for this mechanism, demonstrating high activity and less adverse effects have been ongoing for many years. As a conclusion, it provides clinical use of many new agents in high activity by making appropriate modifications on the chemical structure of topoisomerase II inhibitors obtained herbally or synthetically. In addition, preventing drug resistance frequently seen in cancer patients, targeted treatment and reduced toxicities can be provided with the discovery of new agents. By ensuring that the use of new agents is among the individualized treatment methods, the most appropriate treatment will be provided to the patients.

Keywords

• anticancer,clinical pharmacy,topoisomerase II

TOPOİZOMERAZ II ENZİM İNHİBİTÖRLERİ

Abstract

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.

Sonuç ve Tartışma: Topoizomeraz II enzimi inhibisyonu hedefli kanser kemoterapisi ve bu mekanizmaya uygun, aktivitesi yüksek olup advers etkileri az olan ilaç geliştirme çabaları uzun yıllardır devam eden bir süreçtir. Sonuç olarak, bitkisel veya sentetik olarak elde edilen topoizomeraz II inhibitörlerinin kimyasal yapıları üzerinde uygun modifikasyonların yapılması, yüksek aktivitede birçok yeni ajanın klinik kullanımını mümkün kılmaktadır. Ayrıca kanser hastalarında sıklıkla görülen ilaç direncinin önüne geçilmesi, hedefe yönelik tedavi ve toksisitelerin azaltılması yeni ajanların keşfiyle sağlanabilecektir.Yeni ajanların kullanımının bireyselleştirilmiş tedavi yöntemleri arasında bulunmasının sağlanması ile hastalara en uygun tedavi sunulabilecektir.

Keywords

• antikanser,klinik eczacılık,topoizomeraz II

References

1. 1. Harrington, K. J. (2011). Biology of cancer. Medicine, 39(12), 689-692. https://doi.org/10.1016/j.mpmed.2011.09.015
2. 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. 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. 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. 5. Friedberg, E. C. (2003). DNA damage and repair. Nature, 421(6921), 436-440. https://doi.org/10.1038/nature01408
6. 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. 7. Pommier, Y. (2012). DNA topoisomerases and cancer, Springer, Berlin.
8. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 24. Robert, J. (1993). Clinical pharmacokinetics of idarubicin. Clinical pharmacokinetics, 24(4), 275-288. https://doi.org/10.2165/00003088-199324040-00002
25. 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. 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. 27. Denny, W. A. (2002). Acridine derivatives as chemotherapeutic agents. Current Medicinal Chemistry, 9(18), 1655-1665. https://doi.org/10.2174/0929867023369277
28. 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. 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. 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. 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<215::AID-BIES5>3.0.CO;2-Q
32. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 53. Cresteil, T. (2017). Aclarubicin. In Reference Module in Biomedical Sciences: Elsevier.
54. 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. 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