DNA DAMAGE MECHANISMS OF ANTI-CANCER DRUGS

Yıl 2016, Cilt: 2 Sayı: 1, 33 - 49, 29.06.2016

Bircan Çeken Toptancı Göksel Kızıl Murat Kızıl

https://doi.org/10.23884/mejs/2016.2.1.03

Öz

Organic molecules with DNA-damage ability are of great potential in the development of medicine, toxicology, biochemistry, organic chemistry, biotechnology and gene therapy. DNA damaging agents have historically played a central role in cancer therapy. Even as new approaches to cancer therapy become available, it seems likely that there will be a continued need for the study and development of novel DNA damaging cytotoxins. These agents will see continued use due to their well-establised role in treating various types of cancer and because many of the new approaches to cancer treatment such as immunoteraphy and modulation of the cell cycle are most effective when used in combination with traditional cytotoxins. It is commonly believed that natural products which display potent biological activity are results of natural selection. DNA-damaging natural products frequently possess potent cytotoxic, cytostatic or mutagenic properties and, in nature, may serve as either offensive or defensive weapon in the struggle for survival. Natural products constitute a vast library of organic compounds that can serve as a useful force. A practical reason for the longstanding interest in DNA-damaging natural products is the fact that the cytotoxic or cytostatic effects of these agents sometimes endow them with useful medicinal properties, especially as potential anticancer therapeutics. Several DNA-damaging natural products are currently in use for the treatment of various cancers and others have served as lead compounds in the development of therapeutic agents. Many anti-cancer agents work by alkylating DNA while others destroy DNA by radical chemistry, starting either (i) by abstracting a hydrogen atom from a deoxyribose sugar or (ii) by adding to the alkene pi bond in a base.DNA-damaging agents can be placed into four chemical categories: Intercalators, alkylating agents, DNA strand breakers and groove binders. In this review, DNA damage mechanisms of anti-cancer drugs are 33

discussed.Finally, natural products with extremely potent biological activities sometimes reveal unforeseen biological pathways and these compounds can become useful tools for elucidating the details of complex life processes.

Anahtar Kelimeler

Natural Products, DNA Damage, Anti-Cancer Agents

Kaynakça

• [1] Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., Wlater, P. (2002). Molecular Biology of the Cell, fourth ed. Garland Science, Pp: 120-121. New York, Amsterdam.
• [2] Baraldi, P.G., Preti, D., Fruttarolo, F., Tabrizi, M.A., Romagnoli, R. (2007). Hybrid molecules between distamycin A and active moieties of antitumor agents. Bioorganic and Medicinal Chemistry, 15: 17-35.
• [3] Bennett, R. A. O., Swerdlow, P. S., Povirk, L. F. (1993). Spontaneous cleavage of bleomycin-induced abasic sites in chromatin and their mutagenicity in mammalian shuttle vectors. Biochemistry. 32: 3188-95.
• [4] Beria, I., Baraldi, P.G., Cozzi, P., Caldarelli, M., Geroni, C., Marchini, S., Mongelli, N., Romagnoli, R. (2004). Cytotoxic a-halogenoacrylic derivatives of distamycin A and congeners. Journal of Medicinal Chemistry, 47: 2611-2623.
• [5] Breen, A. P., Murphy, J. A. (1995). Reactions of oxyl radicals with DNA. Free Radical Biology Medicine. 18(6): 1033-77.
• [6] Bignell, G.R., Santarius, T., Pole, J.C.M., Butler, A.P., Perry, J., Pleasance, E., Greenman, C., Menzies, A., Taylor, S., Edkins, S., Campbell, P., Quail, M., Plumb, B., Matthews, L., McLay, K., Edwards, P.A.W., Rogers, J., Wooster, R., Futreal, P.A., Stratton, M.R. (2007). Architectures of somatic genomic rearrangement in human cancer amplicons at sequence level resolution. Genome Research, 17: 1296-1303.
• [7] Caponigro, F., Lorusso, D., Fornari, G., Barone, C., Merlano, M., Airoldi, M., Schena, M., MacArthur, R., Weitman, S., Jannuzzo, M., Crippa, S., Fiorentini, F., Petroccione, A., Comis, S., Phase I. (2010). Dose-escalation study of brostallicin, a minor groove binder, in combination with cisplatin in patients with advanced solid tumors. Cancer Chemotherapy and Pharmacology, 66: 389-394.
• [8] Chargaff, E., Vischer, E., Doniger, R., Green, C., Misani, F. (1949). The composition of the desoxypentose nucleic acids of thymus and spleen. The Journal of Biological Chemistry, 177: 405-416.
• [9] Chambers, A.F., Groom, A.C., MacDonald, I.C. (2002). Metastasis: dissemination and growth of cancer cells in metastatic sites. Nature Reviews Cancer, 2: 563-572.
• [10] Chatterji, T., M. Kızıl, K. Keerthi, G. Chowdhury, T. Pospilis ve K. S. Gates, (2003). Small Molecules That Mimic the Thiol-Triggered Alklating Properties Seen in the Natural Product Leinamycin. Journal of the American Chemical Society.125: 4996-4997.
• [11] Çeken, B. (205). Sentetik maddeler ile DNA kesimi. Doktora Tezi, Fen Bilimleri Enstitüsü, Dicle Üniversitesi, Diyarbakır.
• [12] Çeken, B. (2013). (+)-Duocarmycin Antibiyotiği Analoglarının Sentezlenmesi ve DNA Üzerine Etkilerinin Araştırılması, Doktora Tezi, Fen Bilimleri Enstitüsü, Dicle Üniversitesi, Diyarbakır.
• [13] Fonsega, G.C., Bickelhaupt, F.M., Snijders, J.G., Baerends, E.J. (1999). The nature of the hydrogen bond in DNA base Pairs: the role of charge transfer and resonance assistance. Chemistry-A European Journal, 5: 3581-3594.
• [14] Gao, X., Mirau, P., Patel, D.J. (1992). Structure refinement of the chromomycin dimer- DNA oligomer complex in solution. The Journal of Molecular Biology, 223: 259-279.
• [15] Gnarra, J.R., Tory, K., Weng, Y., Schmidt, L., Wei, M.H., Li, H., Latif, F., Liu, S., Chen, F., Duh, F.M., Lubensky, I., Duan, D.R., Florence, C., Pozzatti, R., Walther, M.M., Bander, N.H., Grossman, H.B., Brauch, H., Pomer, S., Brooks, J.D., Isaacs, W.B., Lerman, M.I., Zbar, B., Linehan, W.M. (1994). Mutations of the VHL tumour suppressor gene in renal carcinoma. Nature Genetics, 7: 85-90.
• [16] Gottesman, M.M., Fojo, T., Bates, S.E., (2002). Multidrug resistance in cancer: role of ATP-dependent transporters. Nature Reviews Cancer, 2: 48-58.
• [17] Harman, D. (1962). Role of free radicals in mutation, cancer, aging, and the maintenance of life. Radiation Research, 16: 753-763.
• [18] Kielkopf, C.L., White, S., Szewczyk, J.W., Turner, J.M., Baird, E.E., Dervan, P.B., Rees, D.C. (1998). A Structural basis for recognition of A.T and T.A base pairs in the minor groove of B-DNA. Science, 282: 111-115.
• [19] Lawley, P. D., Brookes, P. (1963). Further studies on the alkylation of nucleic acids and their constituent nucleotides. Biochemical Journal. 89, 127.
• [20] Lerman, L.S., (1961). Structural Considerations in the Interaction of DNA and Acridines. Journal of Molecular Biology, 3: 18-30.
• [21] Lown, J. W., Sim, S. K., Majumdar, K. C., Chang, R. Y. (1977). Strand scission of DNA by bound adriamycin and daunorubicin in the presence of reducing agents. Biochemical and Biophysical Research Communications. 76: 705.
• [22] Lown, J.W. (1994). DNA recognition by lexitropsins, minor groove binding agents. Journal of Molecular Recognition. 7: 79-88.
• [23] Neidle, S. (2001). DNA minor-groove recognition by small molecules. Natural Product Reports, 18: 291-309.
• [24] Nelson, S.M., Ferguson, L.R,. Denny, W.A. 2007. Non-covalent ligand/DNA interactions: minor groove binding agents. Mutation Research, 623: 24-40.
• [25] Pabo, C.O., Sauer, R.T. (1984). Protein-DNA recognition. Annual Review of Biochemistry, 53: 293-321.
• [26] Pullman, A., Pullman, B. 1981. Molecular electrostatic potential of the nucleic acids. Quarterly Reviews of Biophysics. 14(3): 289-380.
• [27] Sies, H. (1986). Biochemistry of Oxidative Stress. Angew. Chem. Int. Ed. Engl. 25:1058.
• [28] Silverman, R. B. (1991). The Organic Chemistry of Drug Design and Drug Action. Academic Press. ILLINOIS.
• [29] Takeda, Y., Ohlendorf, D.H., Anderson, W.F., Matthews, B.W. 1983. DNA-binding proteins. Science, 221: 1020-1026.
• [30] Tomasz, M. (1995). Mitomycin C: Small, fast and deadly (but very selective). Chemistry and Biology, 2: 575-579.
• [31] Tu S.M. in: S.T. Rosen (Ed.). (2010). Heterogeneity of Cancer, Origin of Cancers, Springer, Pp. 129-136.
• [32] Umezawa H, Maeda K, Takeuchi T, Okami Y. (1966). New antibiotics, bleomycin A and B. J Antibiot (Tokyo). 19(5): 200-9.
• [33] Urruticoechea, A., Alemany, R., Balart, J., Villanueva, A., Viñals, F., Capellá, G. (2010). Recent advances in cancer therapy: an overview. Current Pharmaceutical Design, 16: 3-10.
• [34] Von Sonntag, C., Hagen,U., Schon-Bopp., A., Schulte-Frohlinde, D. (1981). Radiation induced strand breaks in DNA: Chemical and enzymatic analysis of end gropus and mechanistic aspects. Advances in Radiation Biology. 9: 109.
• [35] Watson, J.D., Crick, F.H.C. (1953). A structure for deoxyribose nucleic acid. Nature. 171, 737-738.
• [36] Watson, J.D., Crick, F.H.C. (1993). Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid. The Journal of the American Medical Association. 269: 1966-1967.
• [37] Weiling, F. (1991). Historical study: Johann Gregor Mendel 1822-1884. American Journal of Medical Genetics, 40: 1-25.
• [38] Wing, R., Drew, H., Takano, T., Broka, C., Tanaka, S., Itakura, K., Dickerson, R. (1980). Crystal structure analysis of a complete turn of B-DNA. Nature, 287: 755-758.
• [39] Yap, K.Y.L, Chan, A., Chui, W.K., Chen, Y.Z. (2010). Cancer informatics for the clinician: an interaction database for chemotherapy regimens and antiepileptic drugs. Seizure, 19: 59-67.